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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 1992. Отображено 100.
27-09-2012 дата публикации

Pluripotent stem cell that can be isolated from body tissue

Номер: US20120244129A1
Принадлежит: Individual

Objects of the present invention are to provide a method for directly obtaining pluripotent stem cells which do not have tumorigenic property from body tissue and the thus obtained pluripotent stem cells. The present invention relates to SSEA-3 (+) pluripotent stem cells that can be isolated from body tissue.

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08-11-2012 дата публикации

Nanoparticle loaded stem cells and their use in mri guided hyperthermia

Номер: US20120283503A1
Автор: Lyubov Ostrovska
Принадлежит: JOHNS HOPKINS UNIVERSITY

The present invention provides stem cells loaded with bi-functional magnetic nanoparticles (nanoparticle-loaded stem cells (NLSC)) that both: a) heat in an alternating magnetic field (AMF); and b) provide MRI contrast enhancement for MR-guided hyperthermia. The nanoparticles in the NLSC are non-toxic, and do not alter stem cell proliferation and differentiation, the nanoparticles do however, become heated in an alternating magnetic field, enabling therapeutic applications for cancer treatment. NLSC can deliver hyperthermia to hypoxic areas in tumors for sensitization of those areas to subsequent treatment, thus delivering therapy to the most treatment-resistant tumor regions. The heating of diseased tissue either results in direct cell killing or makes the tumor more susceptible to radio- and/or chemotherapy. The NLSC of the present invention can be used for MR image-guided hyperthermia in oncology, in stem cell research for cell tracking and heating, and for elimination of mis-injected stem cells.

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29-11-2012 дата публикации

Treatment of bone fracture

Номер: US20120301442A1

The use of mesenchymal stem cells cultured in the presence of HS-2 for the treatment of bone fracture. Repair of bone fracture using such cells is enhanced compared with the treatment of bone fracture using mesenchymal cells cultured without HS-2. These mesenchymal stem cells may be formulated in a pharmaceutical composition and injected directly into tissues surrounding the fracture or used in a biocompatible implant or prosthesis.

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07-02-2013 дата публикации

Use of a Proteolytic Enzyme for the Modification of the Cell Surface of a Stem Cell

Номер: US20130034901A1
Принадлежит: SUOMEN PUNAINEN RISTI VERIPALVELU

The present invention relates to a stem cell and/or a population thereof having a specific profile of cell surface proteins and/or proteoglycans. The present invention also relates to use of a proteolytic enzyme in the modification of the cell surface of a stem cell. The present invention further relates to a method of modifying the cell surface of a stem cell by treatment with a proteolytic enzyme.

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13-06-2013 дата публикации

COMBINATIONS OF PROTEINS TO ENHANCE VIABILITY OF STEM CELLS AND THEIR PROGENITORS BEFORE TRANSPLANTATION

Номер: US20130149779A1
Автор: Kiss Zoltan
Принадлежит: ZOLTAN LABORATORIES LLC

Embodiments of the present invention include the use of placental alkaline phosphatase alone or in combination with human transferrin and, optionally, human α-antitrypsin to enhance the proliferation and survival of transplanted stem cells and stem cell-derived progenitor cells. 1. A method for stimulating proliferation and promoting survival of mesenchymal stem cells , or hematopoietic stem cells , or their progenitor cells before transplantation , the method comprising the steps of (i) contacting the mesenchymal stem cells , or hematopoietic stem cells , or their progenitor cells with a first composition comprising 1-50μ per ml of an active PALP in a suitable cell culture medium containing 0-10% serum , and (ii) harvesting said cells for transplantation in a suitable medium supplemented with a second composition comprising an active PALP.2. The method of claim 1 , wherein the first composition claim 1 , or the second composition claim 1 , or both compositions further comprise active transferrin or active α1-antitrypsin claim 1 , or both active transferrin and active α1-antitrypsin.3. The method of claim 1 , wherein the active PALP is a recombinant protein.4. The method of claim 1 , wherein the active PALP is a placental alkaline phosphatase protein derivative.5. The method of claim 2 , wherein active transferrin or active α1-antitrypsin are recombinant proteins.6. The method of claim 1 , wherein the first and second compositions each comprise 1-50 μg/ml of an active PALP.7. The method of claim 2 , wherein the first composition claim 2 , the second composition claim 2 , or both compositions comprise 1-50 μg/ml of active transferrin claim 2 , 50-500 μg/ml of active α1-antitrypsin claim 2 , or both 1-50 μg/ml of active transferrin and 50-500 μg/ml of active α1-antitrypsin.8. The method of claim 1 , wherein the active PALP is pre-incubated at 65-75° C. for 30 minutes before being added to said cells in steps (i) or (ii).9. The method of claim 2 , wherein the active α1 ...

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27-06-2013 дата публикации

TROPOELASTINS AND USES THEREOF

Номер: US20130164340A1
Принадлежит: PROTEIN GENOMICS, INC.

The present invention relates to biocompatible polymeric scaffold materials, methods for making the materials and methods of using the materials. More particularly, the present invention relates to implants and grafts comprising polymeric scaffold materials of cross-linked human tropoelastin polypeptides and methods of making and using the same. In addition, the present invention provides alternatively spliced tropoelastin polynucleotides and polypeptides. 1. A method for repairing , replacing , or regenerating an injured or damaged tissue comprising:(a) providing an amount of one or more tropoelastin polypeptides;(b) casting the tropoelastin polypeptides into a desired shape to form a scaffold;(c) culturing cells on the shaped tropoelastin polymer scaffold to form an implant; and(d) providing the implant to a subject;thereby repairing, replacing, or regenerating the injured or damaged tissue.2. The method of claim 1 , wherein claim 1 , at least one of the one or more tropoelastin polypeptides comprises an alternatively spliced tropoelastin polypeptide.3. The method of claim 2 , wherein the at least one or more alternatively spliced tropoelastin polypeptides comprises an amino acid sequence as set forth in any one of SEQ ID NOs: 2-48.47.-. (canceled)8. The method of claim 1 , wherein the scaffold comprises:a) a resorbable copolymer;(b) a non-resorbable: copolymer; or(c) a combination of both a resorbable and non-resorbable co-polymer.911.-. (canceled)12. The method of claim 8 , wherein the one or more co-polymers comprises a collagen protein.13. The method of claim 1 , wherein the desired shape is a three dimensional shape14. The method of claim 1 , wherein the desired shape is a sheet or a tube.15. The method of claim 1 , wherein the cells comprise stem cells claim 1 , progenitor cells claim 1 , and/or differentiated cells.1643.-. (canceled)44. A polynucleotide comprising a nucleotide sequence as set forth in any one of SEQ ID NOs: 50-86 or a variant thereof.45. ...

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18-07-2013 дата публикации

Maintenance and propagation of mesenchymal stem cells

Номер: US20130183274A1

Various embodiments of the present invention include compositions, materials and methods for maintaining and propagating mammalian mesenchymal stem cells in an undifferentiated state in the absence of feeder cells and applications of the same.

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28-11-2013 дата публикации

METHOD FOR EXPANSION OF STEM CELLS AND THE USE OF SUCH CELLS

Номер: US20130315879A1
Автор: MA Yupo

The present invention demonstrates that SALL4A and SALL4B are strong positive regulators of hematopoetic stem cell expansion. HSCs receiving expression of SALL4A or SALL4B are able to achieve a high-level of expansion. Cultures of SALL4-transduced cells results in extensive HSC expansion with over 1000-fold higher levels than controls within 2 to 3 weeks and expanded HSCs show no or very little maturation. Moreover, the expansion occurs quite rapidly with significant HSC growth in just a few days. In addition, SALL4-induced HSC expansion exhibits no impairment of hematopoietic cell differentiation. SALL4 appears to function in the maintenance of an undifferentiated proliferation state and block cell differentiation for HSCs. 1. A method for expanding a stem cell population , the method comprising providing to the stem cell population a polypeptide having the expansion enhancement activity of a Sal-like (SALL) polypeptide in an amount effective to expand the stem cell population.2. The method of claim 1 , wherein the stem cell is an adult stem cell.3. The method of claim 1 , wherein the stem cell is in or derived from the brain claim 1 , liver claim 1 , heart claim 1 , kidney claim 1 , skin claim 1 , pancreas claim 1 , bladder claim 1 , gall bladder claim 1 , large intestine claim 1 , small intestine claim 1 , stomach claim 1 , skeletal muscle claim 1 , or lung.4. The method of claim 1 , wherein the stem cell is a hematopoietic stem cell.5. The method of claim 4 , wherein the hematopoietic stem cell is in or derived from umbilical cord blood claim 4 , peripheral blood claim 4 , bone marrow claim 4 , or spleen.6. The method of claim 1 , wherein the hematopoietic stem cell is a human stem cell.7. The method of claim 1 , wherein the SALL polypeptide is attached to a transport moiety capable of crossing a cell membrane claim 1 , thereby transporting the SALL polypeptide into the cell.8. The method of claim 7 , wherein the transport moiety is a transactivator of ...

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02-01-2014 дата публикации

Method of purifying exosomes

Номер: US20140004601A1
Автор: Sai Kiang Lim

We describe a method of purifying a mesenchymal stem cell particle such as an exosome, the method comprising separating the mesenchymal stem cell particle on the basis of its negative charge. The method may comprise (a) providing a composition comprising mesenchymal stem cell particles such as a mesenchymal stem cell conditioned medium (MSC-CM); (b) applying the composition comprising mesenchymal stem cell particles to an ion exchange resin to enable mesenchymal stem cell particles to bind to the ion exchange resin; and (c) eluting bound mesenchymal stem cell particles. The ion exchange resin may comprise an anion exchange resin such as an anion exchange spin column.

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20-02-2014 дата публикации

Pdgf induced cell homing

Номер: US20140050771A1
Автор: Jeremy J. Mao, Wenli Zhao
Принадлежит: Columbia University of New York

Provided is a method of causing a cell to migrate to a scaffold. Also provided is a method of treating a mammal that has a tissue defect. Further provided is a tissue scaffold comprising platelet-derived growth factor (PDGF). Additionally, a method of making a tissue scaffold capable of recruiting a cell is provided.

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10-04-2014 дата публикации

Method for obtaining a tissue-engineering product for regeneration of cartilaginous tissue

Номер: US20140099694A1
Принадлежит: BANC DE SANG I TEIXITS

The present invention relates to a method for obtaining a tissue engineering product designed to regenerate cartilage tissue, said product comprising expanded bone marrow mesenchymal cells, a non-cellular matrix and a fibrin gel, the method comprising the steps of: (a) expanding the mesenchymal cells; (b) conjugating the mesenchymal cells to the matrix; (c) washing the product obtained in step (b); and (d) mixing the product obtained in step (c) with a fibrin gel.

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03-01-2019 дата публикации

Method for Inducing Targeted Differentiation of Human Stem Cells Toward Hepatic Cells

Номер: US20190002825A1
Автор: CHEN Li-Xin, ZHANG Pei-Lin
Принадлежит:

The present invention relates to a novel method for multi-target-directed inducing direct differentiation of human stem cells, such as human embryonic stem cells (ES cells) or induced pluripotent stem cells (iPS cells), into hepatocytes using combinations of small molecules. The present invention discloses a medium and a culturing method for inducing directed differentiation of human stem cells into hepatocytes directly. In the method of the present invention, no exogenous genes are need to be introduced into stem cells, no stepwise induction is needed, various cell growth factors are not needed, and directed differentiation of human stem cells into hepatocytes directly can be achieved using only small chemical molecules. The differentiated human hepatocytes obtained have the typical characteristics of human hepatocytes, the differentiated liver precursor cells can be passaged for a long period of time, and the differentiated liver mature cells can be passaged for a limited number of times. Moreover, the method uses a conventional culturing procedure with simple operation, low cost, safety and stability. 1. A medium for inducing directed differentiation of human stem cells into hepatocytes comprising a cell differentiation minimal medium; anda GSK3β inhibitor with a final concentration of 0.5-8 uM;a TGFβ inhibitor with a final concentration of 0.1-10 uM; anda retinoid with a final concentration of 0.001-10 uM;wherein the medium can induce directed differentiation of human stem cells into hepatocytes directly, thereby obtaining human liver precursor cells or liver mature cells.2. The medium according to claim 1 , wherein claim 1 ,the GSK3β inhibitor is present at a final concentration of 0.5-5 uM;the TGFβ inhibitor is present at a final concentration of 0.5-8 uM; andthe retinoid is present at a final concentration of 0.01-5 uM.3. The medium according to claim 1 , wherein the GSK3β inhibitor is selected from GSK3β signaling pathway inhibitors or compounds of the same ...

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03-01-2019 дата публикации

Humanized mouse model of myasthenia gravis and msc therapy

Номер: US20190002832A1

The present invention relates to an animal model of myasthenia gravis, and to uses thereof.

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13-01-2022 дата публикации

MATERIALS AND METHODS FOR TREATMENT OF HEREDITARY HAEMOCHROMATOSIS

Номер: US20220008558A1
Принадлежит:

Materials and methods for treating a patient with hereditary hemochromatosis (HHC), both ex vivo and in vivo, and materials and methods for modulating the expression, function, or activity of a haemochromatosis (HFE) gene in a cell by genome editing. 1. A method for editing a haemochromatosis (HFE) gene in a human cell by genome editing , the method comprising:introducing into the human cell one or more deoxyribonucleic acid (DNA) endonucleases to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near the HFE gene or other DNA sequences that encode regulatory elements of the HFE gene that results in a permanent deletion, insertion, correction, or modulation of expression or function of one or more mutations within or near or affecting the expression or function of the HFE gene and results in restoration of HFE protein activity.2. A method for inserting a haemochromatosis (HFE) gene in a human cell by genome editing , the method comprising:introducing into the human cell one or more deoxyribonucleic acid (DNA) endonucleases to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near a safe harbor locus that results in a permanent insertion of the HFE gene, and results in restoration of HFE protein activity.322.-. (canceled)23. An in vivo method for treating a patient with hereditary hemochromatosis (HHC) , the method comprising the step of editing a haemochromatosis (HFE) gene in a cell of the patient or other DNA sequences that encode regulatory elements of the HFE gene , or editing within or near a safe harbor locus in a cell of the patient.24. The method of claim 23 , wherein the editing step comprises:introducing into the cell one or more deoxyribonucleic acid (DNA) endonucleases to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near the HFE gene or other DNA sequences that encode regulatory elements of the HFE gene that results in a permanent ...

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14-01-2021 дата публикации

METHOD FOR ENHANCING MIGRATION OF STEM CELLS INTO CANCER CELLS

Номер: US20210008118A1

The present invention relates to a method for improving the migration ability of stem cells into cancer cells comprising educating the stem cells by treating the stem cells with an in vitro cell culture medium of cancer cells obtained from a cancer patient to be treated and optionally an anionic channel activator. 1. A method of improving the migration ability of stem cells into cancer cells comprising:educating the stem cells by treating the stem cells with a cell culture medium of in vitro cell culture of cancer cells obtained from a cancer patient to be treated and optionally an anion channel activator.2. The method of claim 1 , wherein the stem cells are embryonic stem cells or mesenchymal stem cells.3. The method of claim 2 , wherein the mesenchymal stem cells are bone marrow-derived mesenchymal stem cells claim 2 , adipose-derived mesenchymal stem cells claim 2 , umbilical cord-derived mesenchymal stem cells claim 2 , dental pulp-derived stem cells or peripheral blood-derived stem cells.4. The method of claim 1 , wherein the anion channel activator is Cl channel activator or bicarbonate channel activator.5. The method of claim 1 , wherein the anion channel activator is forskolin claim 1 , denufosol claim 1 , brevenal claim 1 , lubiprostone claim 1 , N-aroylaminothiazole “activators” (E) analogue.6. A composition comprising an anion channel activator and a cell culture medium of in vitro cell culture of cancer cells obtained from a cancer patient to be treated as an active ingredient.7. The composition of claim 6 , wherein the stem cells are embryonic stem cells or mesenchymal stem cells.8. The composition of claim 7 , wherein the mesenchymal stem cells are bone marrow-derived mesenchymal stem cells claim 7 , adipose-derived mesenchymal stem cells claim 7 , umbilical cord-derived mesenchymal stem cells claim 7 , dental pulp-derived stem cells or peripheral blood-derived stem cells.9. The composition of claim 6 , wherein the anion channel activator is a Cl ...

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08-01-2015 дата публикации

Novel MSC Surface Marker

Номер: US20150010516A1
Принадлежит:

The present invention relates to the use of at least one antibody which binds to the SUSD2 antigen, or to functional fragments of the antibody, in combination with at least one of the following: an antibody which binds to CD140b, an antibody which binds to CD56, and/or an antibody which binds to TNAP, or functional fragments thereof, for isolation of mesenchymal stem cells, especially those having particularly chondrocytic and osteogenic differentiation potential. The invention further relates to processes for isolating such stem cells using these antibodies 1. Method for the isolation and/or identification of mesenchymal stem cells with chondrocyte differentiation potential , the method comprising the following steps:a) contacting a sample which contains mesenchymal stem cells with at least one antibody which binds to the antigen SUSD2 (Sushi domain containing protein 2), or with functional fragments of the antibody,b) optionally contacting the sample with a further antibody which binds to the antigen SUSD2, or with functional fragments of the antibody,c) contacting the sample with at least one antibody which binds to CD140b, CD56 and/or TNAP, or with functional fragments of the antibody, and/ord) identifying the cells in the sample which bind i) the at least one antibody or fragments thereof which binds to the antigen SUSD2 and ii) the at least one antibody which binds to CD140b, CD56 and/or TNAP, thereby isolating and/or identifying mesenchymal stem cells with chondrocyte differentiation potential.2. The method as claimed in claim 1 , wherein the anti-SUSD2 antibody used in step a) is selected from the group consisting of at least one of the following:the antibody W5C5 which is produced by the cell line deposited at the German Collection of Microorganisms and Cell Cultures with the No. ACC2813,the antibody W3D5 which is produced by the cell line deposited at the German Collection of Microorganisms and Cell Cultures with the No. ACC2815,functional fragments of the ...

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12-01-2017 дата публикации

Biophysically Sorted Osteoprogenitors From Culture Expanded Bone Marrow Derived Mesenchymal Stromal Cells (MSCs)

Номер: US20170009208A1
Принадлежит:

The invention provides, inter alia, populations of large mesenchymal stem cells (MSC)(as well as conditioned medium from these cells) with enhanced regenerative potential, as well as methods of culturing and using these populations, such as therapeutic methods of mediating tissue repair or enhancing homing and engraftment of hematopoietic stem cells. These large MSC populations can, in certain embodiments, be produced by biophysically sorting an MSC-containing population. 1. A method of producing an MSC population with enhanced regenerative potential , comprising:a) culturing an MSC-containing population of cells in a culture medium to a confluence of 80% to 90% over each of at least four population doublings to provide a population enriched in large-MSC cells, wherein the four population doublings are measured from initial extraction of the MSC-containing population from a source; andb) biophysically sorting the MSC-containing population of cells produced in step (a) and collecting a large-MSC population of cells from the MSC-containing population, thereby producing an MSC population with enhanced regenerative potential.2. The method of claim 1 , wherein the biophysical sorting of the MSC-containing population comprises applying the MSC-containing population of cells to an inlet of an MSC-dimensioned microfluidic device and collecting a large-MSC population of cells from an outlet of the MSC-dimensioned microfluidic device.3. The method of claim 1 , further comprising culturing the large-MSC population.4. The method of claim 3 , comprising collecting conditioned medium from the large-MSC culture.5. The method of claim 4 , wherein the large-MSC culture medium contains increased amounts of one or more of IL-6 claim 4 , IL-8 claim 4 , MCP-1 claim 4 , EGF claim 4 , VEGF claim 4 , FGF1 claim 4 , FGF2 claim 4 , BMP2 claim 4 , ANG1 claim 4 , osteopontin claim 4 , Igfbp2 claim 4 , Angptl2 claim 4 , Angptl3 claim 4 , and Angptl15 compared to a culture medium obtained from ...

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10-01-2019 дата публикации

TREATMENT OF PULMONARY ARTERIAL HYPERTENSION WITH MESENCHYMAL STEM CELLS

Номер: US20190008904A1
Принадлежит: United Therapeutics Corporation

The application is directed to a method for treating or preventing vasculopathy comprising administrating to a subject in need thereof a pharmaceutical composition comprising mesenchymal precursor cells (MPCs) and a prostacyclin. Also provided a method for treating or preventing vasculopathy in a subject in need thereof, comprising administering to the subject a prostacyclin and a mesenchymal stem cell (MSC) or a MSC-conditioned culture medium or administering to the subject a MSC or a MSC-conditioned culture medium that has treated with prostacyclin. Pharmaceutical compositions suitable for such treatments are also provided. 1. A method for treating or preventing vasculopathy comprising administrating to a subject in need thereof a pharmaceutical composition comprising mesenchymal precursor cells (MPCs) and a prostacyclin.2. The method of claim 1 , wherein the subject is a human being.3. The method of claim 1 , wherein the MPCs are obtained from bone marrow of the subject.4. (canceled)5. The method of claim 1 , wherein the pharmaceutical composition further comprises at least one pharmaceutically-acceptable carrier.6. The method of claim 1 , wherein the pharmaceutical composition further comprises at least one therapeutic agent.7. The method of claim 1 , wherein the subject is suffering from pulmonary hypertension.8. The method of claim 1 , wherein the subject is suffering from peripheral vascular disease (PVD) claim 1 , critical limb ischemia (CLI) claim 1 , coronary artery disease claim 1 , and/or diabetic vasculopathy.911-. (canceled)12. The method of claim 7 , further comprising reducing thrombosis in pulmonary arteries claim 7 , reducing inflammation in pulmonary arteries claim 7 , reducing the proliferation of intimal smooth muscle in pulmonary arteries claim 7 , and/or reducing the formation of plexiform lesions in pulmonary arteries.1315-. (canceled)16. The method of claim 7 , further comprising increasing the amount of nitric oxide in pulmonary arteries ...

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08-01-2015 дата публикации

SYNTHETIC ATTACHMENT MEDIUM FOR CELL CULTURE

Номер: US20150010999A1
Принадлежит:

An aqueous cell culture medium composition includes an aqueous cell culture solution configured to support the culture of mammalian cells. The composition further includes a synthetic polymer conjugated to a polypeptide dissolved in the aqueous cell culture solution. The synthetic polymer conjugated to a polypeptide is configured to attach to the surface of a cell culture article under cell culture conditions. Incubation of the aqueous cell culture medium composition on a cell culture surface under cell culture conditions results is attachment to the surface of the synthetic polymer conjugated to the polypeptide. 1. An aqueous cell culture medium composition , comprising:an aqueous cell culture solution configured to support the culture of mammalian cells; and 'wherein the synthetic polymer conjugated to a polypeptide is configured to attach to the surface of a cell culture article under cell culture conditions, and', 'a synthetic polymer conjugated to a polypeptide dissolved in the aqueous cell culture solution;'}wherein incubation of the aqueous cell culture medium composition on a cell culture surface under cell culture conditions results in attachment to the surface of the synthetic polymer conjugated to the polypeptide.2. The composition of claim 1 , wherein the cell culture medium composition is a chemically defined composition.3. The composition of claim 1 , wherein the polymer has a linear backbone and is crosslink free claim 1 , wherein the synthetic polymer conjugated to the polypeptide is soluble in water at 20° C. or less claim 1 , andwherein the composition is substantially free of organic solvents.4. The composition of claim 1 , wherein the polymer is formed from at least one monomer comprising a conjugated polypeptide.5. The composition of claim 4 , wherein the at least one monomer comprising a conjugated polypeptide is methacrylic acid.6. The composition of claim 1 , wherein the polymer is formed from polymerization of (i) methacrylic acid conjugated ...

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09-01-2020 дата публикации

PERINATAL TISSUE DERIVED MESENCHYMAL STEM CELLS: METHOD OF PREPARATION AND USES THEREOF

Номер: US20200009193A1
Принадлежит:

The present invention discloses the preparation of placenta tissue derived CD106CD151+Nestin+ mesenchymal stem cells (MSCs). In a first aspect, the invention relates to a particular method to prepare these cells at industrial scale and the cell population generated thereby. In a second aspect, the invention relates to a cell culture obtained by said particular method, containing placental CD106CD151+Nestin+ MSCs expressing the vascular cell adhesion molecule 1 (VCAM-1) marker. The present application shows that said placental CD106CD151+Nestin+ MSCs are capable of inducing angiogenesis in vitro and in vivo. The herein presented results also show that administering said placental CD106CD151+Nestin+ MSCs to individuals suffering from an ischemic disease or from a disorder of the circulatory system results in a detectable improvement of one or more symptoms of said disease or disorder. Therefore, in a third aspect, the invention relates to placental CD 106CD151+Nestin+ MSCs for use as a medicament for treating subjects suffering from an ischemic disease, a disorder of the circulatory system, an immune disease, an organ injury or an organ function failure. 136-. (canceled)37. A method to prepare CD106CD151+Nestin+ mesenchymal stem cells (MSCs) , said method comprising culturing a population of undifferentiated MSCs in a culture medium comprising at least two pro-inflammatory growth factors.38. The method of claim 37 , wherein said pro-inflammatory growth factors are IL1β and IL4.39. The method of claim 37 , wherein said undifferentiated MSCs are obtained by cell isolation from an explant of umbilical cord fragment or by cell isolation from a placenta tissue fragment.40. The method of claim 37 , wherein said culture medium contains between 1 and 100 ng/ml of Interleukine 1β.41. The method of claim 37 , wherein said culture medium contains between 1 and 100 ng/ml of Interleukine 4.42. A method to enhance the CD106 expression level of undifferenciated MSCs claim 37 , said ...

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08-01-2015 дата публикации

CULTURE MEDIUM FOR PROLIFERATING STEM CELL, WHICH CONTAINS SULFATED COMPOUND

Номер: US20150011003A1
Принадлежит: AJINOMOTO CO., INC.

A medium which comprises a fibroblast growth factor (FGF), and a sulfated compound or a pharmaceutically acceptable salt thereof at a concentration which promotes the growth of a stem cell in the presence of FGF, is useful for culturing stem cells. 1. A medium for stem cell proliferation , comprising a fibroblast growth factor (FGF) , and a sulfated compound or a pharmaceutically acceptable salt thereof at a concentration promoting the growth of a stem cell in the presence of FGF , wherein the sulfated compound content is not more than 250 ng/ml when the sulfated compound is a sulfated polysaccharide.2. The medium according to claim 1 , wherein the sulfated compound or pharmaceutically acceptable salt thereof is sulfated saccharide or a pharmaceutically acceptable salt thereof claim 1 , wherein the sulfated saccharide content is not more than 250 ng/ml when the sulfated saccharide is a sulfated polysaccharide.4. The medium according to claim 2 , wherein the sulfated saccharide or pharmaceutically acceptable salt thereof is at least one compound selected from the group consisting of a sulfated monosaccharide claim 2 , a sulfated disaccharide claim 2 , a sulfated polysaccharide claim 2 , a sulfated sugar alcohol claim 2 , and a sulfated cyclitol claim 2 ,or a pharmaceutically acceptable salt of said at least one compound.5. The medium according to claim 2 , wherein the content level of sulfur in said sulfated saccharide or pharmaceutically acceptable salt thereof is not less than 5 wt %.6. The medium according to claim 2 , wherein said sulfated saccharide or pharmaceutically acceptable salt thereof is at least one member selected from the group consisting of dextran sulfate Na claim 2 , cellulose SONa claim 2 , xanthan gum SONa claim 2 , pectin SONa claim 2 , fucoidan claim 2 , alginate SONa claim 2 , inulin SONa claim 2 , maltoheptaose SONa claim 2 , stachyose SONa claim 2 , maltotriose SONa claim 2 , maltitol SONa claim 2 , sucrose 8SOK claim 2 , glucose SONa claim ...

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11-01-2018 дата публикации

ISOLATION OF ADULT MULTIPOTENTIAL CELLS BY TISSUE NON-SPECIFIC ALKALINE PHOSPHATASE

Номер: US20180009905A1
Принадлежит: MESOBLAST, INC.

The present invention relates to the use of tissue non-specific alkaline phosphatase (TNAP) as a marker for identifying and/or isolating adult multipotential cells. The present invention also relates to cell populations enriched by methods of the present invention and therapeutic uses of these cells. 145-. (canceled)46. An enriched population of TNAP adult multipotential cells , wherein at least 4% of the total cell population are TNAP , STRO-1 multipotential cells capable of being cultured in vitro to produce adipocytes , osteocytes and chondrocytes , wherein the TNAP marker is a TNAP marker which binds the STRO-3 antibody produced by the hybridoma cell line deposited under ATCC Accession Number PTA-5582.47. An enriched population according to claim 46 , wherein at least 10% of the total cell population are TNAP claim 46 , STRO-1 multipotential cells capable of being cultured in vitro to produce adipocytes claim 46 , osteocytes and chondrocytes.48. An enriched population according to claim 46 , wherein at least 20% of the total cell population are TNAP claim 46 , STRO-1 multipotential cells capable of being cultured in vitro to produce adipocytes claim 46 , osteocytes and chondrocytes.49. An enriched population according to claim 46 , wherein the STRO-1 cells are STRO-1.50. An enriched population according to claim 47 , wherein the STRO-1 cells are STRO-1.51. An enriched population according to claim 48 , wherein the STRO-1 cells are STRO-1.52. A method of generating a committed cell population of a specific tissue type claim 46 , the method comprising culturing a population of adult multipotential cells according to in the presence of one or more stimulatory factors; and subjecting said cultured population to conditions biasing differentiation of the adult muitipotential cells to the specific tissue type.53. A method of generating a committed cell population of a specific tissue type claim 47 , the method comprising culturing a population of adult multipotential ...

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03-02-2022 дата публикации

Genetically modified mesenchymal stem cell expressing klotho

Номер: US20220033779A1
Принадлежит: Apceth GmbH and Co KG

A genetically modified mesenchymal stem cell including an exogenous nucleic acid including a Klotho encoding region operably linked to a promoter or promoter/enhancer combination, wherein the genetically modified mesenchymal stem cell exhibits increased Klotho expression compared to an unmodified mesenchymal stem cell. Also disclosed are methods of treating a patient including administering a therapeutically effective number of the genetically modified mesenchymal stem cells to the patient. The methods of treatment include treating the patient for a neurodegenerative disease; cancer; organ fibrosis; renal disease; age-related changes of organs or organ systems; to slow, reverse and/or inhibit aging; arteriosclerosis; dementia; diabetes mellitus; erectile dysfunction; autoimmune diseases or autoimmune-related diseases; an inflammatory disease of the lung and sepsis.

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15-01-2015 дата публикации

Mesenchymal Stem Cells and Uses Therefor

Номер: US20150017132A1
Принадлежит:

Methods of treating autoimmune diseases, allergic responses, cancer, or inflammatory diseases in an animal, promoting would healing, repairing epithelial damage and promoting angiogenesis in an organ or tissue of an animal by administering to the animal mesenchymal stem cells in an effective amount. 113-. (canceled)14. A method of reducing inflammation in the gastrointestinal track of a patient in need thereof , comprising the step of intravenously or intraarterially administering to a human suffering from inflammation of the gastrointestinal track a suspension of cells in an amount effective to reduce the inflammation , wherein the cells are allogeneic mesenchymal stem cells , wherein the suspension of mesenchymal stem cells is at least 95% homogeneous and wherein the mesenchymal stem cells express CD73 and CD105.15. The method of claim 14 , wherein the patient suffers from Crohn's disease claim 14 , inflammatory bowel disease claim 14 , gastrointestinal graft-versus-host disease (GVHD) claim 14 , or autoimmune gastritis.16. The method of claim 15 , wherein the patient suffers from gastrointestinal graft-versus-host disease.17. The method of claim 16 , wherein the patient was refractory to one or more treatments to GVHD.18. The method of claim 14 , wherein the suspension further comprises an acceptable pharmaceutical carrier.19. The method of claim 18 , wherein the acceptable pharmaceutical carrier is a pharmaceutically acceptable liquid medium for injection.20. The method of claim 14 , wherein the suspension is administered in an amount of from about 1×10cells/kg to about 1×10cells/kg.21. The method of claim 14 , wherein the suspension is administered in an amount of from about 1×10cells/kg to about 5×10cells/kg.22. The method of claim 14 , wherein the suspension is administered in an amount of about 3×10cells/kg.23. The method of claim 14 , wherein the method comprises increasing production or secretion of an anti-inflammatory cytokines interleukin-4 or ...

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18-01-2018 дата публикации

Adult Stem Cells/Progenitor Cells and Stem Cell Proteins for Treatment of Eye Injuries and Diseases

Номер: US20180015124A1
Принадлежит:

The present invention encompasses methods and compositions for treating an ocular disease, disorder or condition in a mammal. The invention includes a population of mesenchymal stromal cells that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties. The invention includes administration of TSG-6, STC-1, or a combination thereof to the ocular as a treatment for an ocular disease, disorder or condition in a mammal. 145-. (canceled)46. A method of treating uveitis in a patient , comprising:administering to said patient a therapeutic agent comprising TSG-6 protein or a biologically active fragment, or variant thereof, wherein said TSG-6 protein or biologically active fragment, or variant thereof, is administered in an amount effective to treat said uveitis in said patient.47. The method of wherein said TSG-6 protein or a biologically active fragment claim 46 , or variant thereof claim 46 , is administered to said patient in an amount of from about 0.01 mg to about 20 mg per kilogram of body weight.48. The method of wherein said TSG-6 protein or a biologically active fragment claim 47 , or variant thereof claim 47 , is administered to said patient in an amount of from about 0.1 mg to about 5 mg per kilogram of body weight.49. The method of wherein said therapeutic agent is administered intraocularly.50. A method of treating uveitis in a patient claim 46 , comprising:administering to the eye of said patient eye drops containing a therapeutic agent comprising TSG-6 protein or a biologically active fragment, or variant thereof, and wherein said TSG-6 protein or biologically active fragment, or variant thereof, is contained in said eye drops in an amount effective to treat said uveitis in said patient.51. The method of wherein said therapeutic agent further comprises at least one anti-infective agent.52. The method of wherein said at least one anti-infective agent is at least one anti-bacterial agent.53. The method of wherein said at ...

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19-01-2017 дата публикации

GENETICALLY MODIFIED MESENCHYMAL STEM CELLS THAT EXPRESS AN EXOGENOUS CYTOTOXIC PROTEIN

Номер: US20170015976A1
Автор: NELSON Peter J.
Принадлежит:

This invention provides a method for treating a subject afflicted with a tumor using genetically modified mesenchymal stem cells, wherein each genetically modified mesenchymal stem cell contains an exogenous nucleic acid comprising (i) a cytotoxic protein-encoding region operably linked to (ii) a promoter or promoter/enhancer combination, whereby the cytotoxic protein is selectively expressed when the genetically modified mesenchymal stem cells come into proximity with the tumor's stromal tissue. This invention further provides genetically modified mesenchymal stem cells for use in this method. 1. A method for treating a subject afflicted with a tumor comprising introducing into the subject's bloodstream a therapeutically effective number of genetically modified mesenchymal stem cells , wherein each genetically modified mesenchymal stem cell comprises an exogenous nucleic acid comprising (i) a cytotoxic protein-encoding region operably linked to (ii) a promoter or promoter/enhancer combination , wherein the promoter or promoter/enhancer combination is inducible by inflammatory mediators.2. The method of claim 1 , wherein the promoter or promoter/enhancer combination is inducible by cytokines.3. The method of claim 1 , wherein the inflammatory mediator is selected from the group consisting of TNF-alpha claim 1 , IFN-gamma claim 1 , IL-6 claim 1 , TGF-beta claim 1 , IL-10 claim 1 , M-CSF and IL1β.4. The method of claim 1 , wherein the promoter or promoter/enhancer combination comprises an NF-kβ-responsive element or a Smad-binding element.5. The method of claim 1 , wherein the promoter is the RANTES promoter.6. The method of claim 1 , wherein the subject is human.7. The method of claim 1 , wherein the genetically modified mesenchymal stem cells are CD34 stem cells.8. The method of claim 1 , wherein the genetically modified mesenchymal stem cells are allogenic with respect to the subject.9. The method of claim 1 , wherein the genetically modified mesenchymal stem cells ...

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18-01-2018 дата публикации

METHOD FOR PREPARING PLURIPOTENT STEM CELLS

Номер: US20180016549A1
Принадлежит: OTSUKA PHARMACEUTICAL FACTORY, INC.

An object of the present invention is to provide a method capable of inexpensively and conveniently preparing cells having pluripotency and a very low risk of tumorigenic transformation. The cells can be prepared by suspension-culturing mammalian mesenchymal stem cells such as human mesenchymal stem cells from bone marrow (hMSC-BM) and human adipose tissue-derived mesenchymal stem cells (hAT-MSC) (also referred to as “human adipose-derived stem cells [hADSC]”), 7 types of human adherent mature cells (human hepatocyte cells [hHEP cells], human umbilical vein endothelial cells [HUVEC cells], human dermal lymphatic microvascular endothelial cells [HMVEC cells], human epidermal keratinocyte cells [NHEK cells], human bronchial epithelial cells [NHBE cells], human melanocyte cells [NHEM cells], and human smooth muscle cells [UASMC cells]), and 3 types of human adherent precursor cells (human dermal fibroblast cells [NHDF cells], human skeletal muscle myoblast cells [HSMM cells], and human osteoblast cells [NHOst cells]) to form cell masses (spheroids). 1. A method for preparing a pluripotent stem cell , comprising spheroid-culturing mammalian mesenchymal stem cells to form a spheroid of pluripotent stem cells , wherein the spheroid-culturing is performed in a physiological aqueous solution free from serum or a serum substitute.2. The method according to claim 1 , wherein the mammalian mesenchymal stem cells are human mesenchymal stem cells from bone marrow or human adipose tissue-derived mesenchymal stem cells.3. The method according to claim 1 , wherein the pluripotent stem cell expresses Nanog claim 1 , Oct3/4 claim 1 , or Sox2.4. The method according to claim 2 , wherein the pluripotent stem cell expresses Nanog claim 2 , Oct3/4 claim 2 , or Sox2. This application is a divisional application of the pending U.S. application Ser. No. 14/913,707 filed on Feb. 23, 2016, which is U.S. National Stage of International Application No. PCT/JP2014/004524 filed Sep. 3, 2014, ...

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19-01-2017 дата публикации

CELL-SURFACE MARKER OF EARLY MSC AGING

Номер: US20170016898A1
Автор: OConnor Kim C.

This invention relates to a cell-surface marker for identifying MSC that are aging. This invention also relates to a method of screening MSCs of low proliferation potential and trilineage potential by removing CD264+ MSCs from the population. 1. A method of identifying multipotent mesenchymal stem cells of high proliferation potential , comprising the steps of:a) collecting mesenchymal stem cells;b) measuring the expression of CD264 in collected mesenchymal stem cells; andc) removing the mesenchymal stem cells with positive expression of CD264.2. The method of claim 1 , wherein the step c) is carried out through using fluorescence-activated cell sorting.3. The method of claim 1 , further comprising:{'b': '1', 'b-) measuring the expression of p21; and'}{'b': '1', 'c-) removing the collected mesenchymal stem cells with positive expression of p21.'}4. A method of identifying multipotent mesenchymal stem cells capable of high proliferation comprising the steps of:a) collecting mesenchymal stem cells;b) introducing fluorescent antibodies against CD264 to the collected mesenchymal stem cells;c) sorting the mesenchymal stem cells based on fluorescent characteristics thereof; andd) collecting the mesenchymal stem cells that are not bound by the fluorescent antibodies.5. A composition comprising a population of mesenchymal stem cells having a colony forming efficiency of greater than 35% claim 1 , wherein at least 50% of said mesenchymal stem cells having negative expression of CD264.6. The composition of claim 5 , wherein said mesenchymal stem cells having at least 3-fold trilineage potential relative to mesenchymal stem cells having positive expression of CD264.7. The composition of claim 6 , wherein the mesenchymal stem cells produce 3-fold more mineralization relative to mesenchymal stem cells having positive expression of CD264.8. The composition of claim 6 , wherein the mesenchymal stem cells produce 3-fold more lipids relative to mesenchymal stem cells having positive ...

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17-01-2019 дата публикации

CELL REPROGRAMMING

Номер: US20190017032A1
Принадлежит:

The invention relates to methods and compositions for converting one cell type to another cell type. Specifically, the invention relates to transdifferentiation of a cell to a different cell type. The invention relates to a method for determining the transcription factors required for conversion of a source cell to a cell exhibiting at least one characteristic of a target cell type. The invention also relates to method of reprogramming or forward programming a source cell. 1. A method for determining the transcription factors required for conversion of a source cell to a cell exhibiting at least one characteristic of a target cell type , the method comprising the steps of:determining differential expression of genes in the source and target cell types;determining a network score for each transcription factor (TF) in each of the source and target cell types based on the differential gene expression over at least one network, wherein the network contains information of interactions that affect gene expression;ranking the TFs based on a combination of network scores and differential gene expression information, thereby identifying the set of transcription factors for a conversion from a source cell to a cell exhibiting at least one characteristic of a target cell type.2. A method according to claim 1 , wherein a gene score is determined for each differentially expressed gene in the source and target cell types.3. A method according to or claim 1 , wherein the gene score is a combination of the log fold change and adjusted P− value of the differential expression.4. A method according to any one of to claim 1 , wherein the gene score is calculated using a tree-based method claim 1 , preferably against a background.5. A method according to any one of to claim 1 , wherein the network contains information of protein-DNA interactions claim 1 , protein-DNA and/or protein-RNA interactions.6. A method according to claim 5 , wherein the network contains information of the ...

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28-01-2016 дата публикации

CLOSED SYSTEM SEPARATION OF ADHERENT BONE MARROW STEM CELLS FOR REGENERATIVE MEDICINE APPLICATIONS

Номер: US20160022739A1
Автор: Sabaawy Hatem
Принадлежит:

A method for isolating and processing bone marrow derived stem cells, including the steps of: (a) collecting a biological sample containing adherent bone marrow stem cells in a receptacle with interior walls coated with a cell-adherent substrate; (b) incubating the bone marrow cells on the adherent substrate so that a layer of adherent bone marrow stem cells adheres to the substrate; (c) washing any non-adherent cells from the substrate; and (d) collecting the bone marrow stem cell layer. Isolation kits and use of bone marrow cells harvested for cell therapies are also described. 1. A method for isolating and processing bone marrow derived stem cells comprising the steps of:(a) collecting a biological sample containing adherent bone marrow stem cells in a receptacle with interior walls coated with a cell-adherent substrate;(b) incubating the bone marrow cells on the adherent substrate so that a layer of adherent bone marrow stem cells adheres to the substrate;(c) washing any non-adherent cells from said substrate; and(d) collecting said bone marrow stem cell layer.2. The method of claim 1 , wherein said biological sample comprises red blood cells and the step of collecting a biological sample further includes the step of:receiving from a subject a biological sample containing red blood cells and bone marrow stem cells and separating the red blood cells from the biological sample before the bone marrow stem cells are incubated.3. The method of claim 1 , wherein said sample is autologous.4. The method of wherein said biological sample comprises umbilical cord blood or bone marrow aspirates.5. The method of claim 1 , wherein said cell-adherent substrate comprises a polymeric substrate coated with a cell-adherent biopolymer claim 1 , polypeptide claim 1 , protein or polysaccharide.6. The method of claim 5 , wherein said polymer is corona discharge treated prior to coating with said cell-adherent biopolymer claim 5 , polypeptide claim 5 , protein or polysaccharide.7. The ...

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22-01-2015 дата публикации

Cell Expansion System and Methods of Use

Номер: US20150024492A1
Автор: ANTWILER Glen Delbert
Принадлежит: TERUMO BCT, INC.

Cell expansion systems and methods of use are provided. The cell expansion systems generally include a hollow fiber cell growth chamber, and first and second circulation loops (intracapillary loops and extracapillary loops) associated with the interior of the hollow fibers and exterior of the hollow fibers, respectively. Detachable flow circuits and methods of expanding cells are also provided. 122.-. (canceled)23. A method of expanding cells in a detachable flow circuit configured to attach to a fixed portion of a cell expansion system , wherein the cell expansion system comprises an incubator and a plurality of controllers , the method comprising: a first fluid circulation path comprising a first fluid flow path having at least opposing ends, a first end of the first fluid flow path configured to fluidly associate with a first inlet port of a cell growth chamber, and a second opposing end of the first fluid flow path configured to fluidly associate with a first outlet port of the cell growth chamber, wherein a portion of the first fluid circulation path is configured to be disposably mounted to a first fluid controller of the fixed portion of the cell expansion system;', 'a second fluid circulation path comprising a second fluid flow path having at least opposing ends, a first end of the second fluid flow path configured to fluidly associate with a second inlet of the cell growth chamber, and a second opposing end of the second fluid flow path configured to fluidly associate with a second outlet of the cell growth chamber, wherein a portion of the second fluid circulation path is configured to be disposably mounted to a second fluid controller of the fixed portion of the cell expansion system; and, 'adding the cells to the detachable flow circuit, wherein the detachable flow circuit comprisesincubating the cells to produce an expanded population of cells.24. The method of claim 23 , further comprising harvesting at least a portion of the expanded population of ...

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22-01-2015 дата публикации

DEFINED CELL CULTURING SURFACES AND METHODS OF USE

Номер: US20150024494A1
Принадлежит:

In one aspect, there is provided a cell culturing substrate including: 1. A cell culturing substrate comprising:a cell culture surface having a film attached thereto, wherein said film comprises one or more plasma polymerized monomers; anda coating on said film-coated surface comprising one or more extracellular matrix proteins.2. The cell culturing substrate of claim 1 , wherein said one or more monomers is selected from the group consisting of acrylic acid claim 1 , methacrylic acid claim 1 , acetic acid claim 1 , vinylacetic acid and combinations thereof.3. The cell culturing substrate of claim 1 , wherein said one or more monomers is selected from the group consisting of allylamine claim 1 , methylamine claim 1 , propylamine claim 1 , heptylamine and diaminopropane.4. The cell culturing substrate of claim 1 , wherein said one or more monomers is selected from the group consisting of alkanes claim 1 , alkenes claim 1 , dienes claim 1 , styrenes and combinations thereof.5. The cell culturing substrate of claim 1 , wherein said one or more monomers is selected from the group consisting of amines claim 1 , hydrocarbons and combinations thereof claim 1 , wherein the ratio of amine to hydrocarbon is between about 100:0 and about 20:80.6. The cell culturing substrate of claim 1 , wherein the extracellular matrix proteins are selected from the group consisting of natural claim 1 , recombinant claim 1 , synthetic extracellular matrix proteins and combinations thereof.7. The cell culturing substrate of claim 1 , wherein the coating comprises a whole extracellular matrix protein or a fragment of the extracellular matrix protein.8. The cell culturing substrate of claim 1 , wherein the coating further comprises a component selected from the group consisting of entactin claim 1 , heparan sulfate proteoglycans (HSPG) claim 1 , growth factors and combinations thereof.9. The cell culturing substrate of claim 1 , wherein the cell culture surface comprises a plastic selected from ...

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26-01-2017 дата публикации

EXPANSION OF STEM CELLS IN HOLLOW FIBER BIOREACTORS

Номер: US20170022472A1
Принадлежит: ReGenesys BVBA

The invention is directed to producing large numbers of cells using hollow fiber bioreactor technology. The cells are non-embryonic stem, non-germ cells that can be characterized by one or more of the following: extended replication in culture and markers of extended replication, such as telomerase, markers of pluripotentiality, and broad differentiation potential, without being transformed. 1. A method of expanding cells ex vivo , the method comprising the steps of: a) seeding the cells on a hollow fiber substrate so that the cells adhere to the substrate; b) expanding the adhered cells on the substrate; and c) removing the expanded cells from the substrate , wherein the cells are non-embryonic stem , non-germ cells , wherein the cells express telomerase , are not transformed , and have a normal karotype.2. The method of further comprising d) reseeding the removed cells on the same or different substrate; and e) repeating steps b)-d) until a desired number of expanded cells is reached.3. The method of further comprising administering the removed cells to a subject.4. The method of in which the hollow fiber substrate is in a closed continuous perfusion bioreactor.5. The method of in which the cells are expanded about 10-100 fold.6. The method of - wherein the hollow fiber is coated.7. The method of wherein the coating is fibronectin.8. The method of wherein the wall material in fiber is PA/PAES/PVP.9. The method of - wherein the cells in step (a) comprise a substantially homogeneous population.10. The method of - wherein step (a) comprises seeding cells from a tissue claim 7 , the tissue selected from bone marrow claim 7 , umbilical cord blood claim 7 , umbilical cord matrix claim 7 , peripheral blood claim 7 , placenta claim 7 , placental blood claim 7 , muscle claim 7 , brain claim 7 , kidney claim 7 , or other solid organs.11. The method of wherein the non-embryonic stem claim 1 , non-germ cells further express one or more of oct4 claim 1 , rex-1 claim 1 , rox-1 ...

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10-02-2022 дата публикации

Adult Stem Cell Line Introduced with Hepatocyte Growth Factor Gene and Neurogenic Transcription Factor Gene with Basic Helix-Loop-Helix Motif and Uses Thereof

Номер: US20220042037A9
Принадлежит:

The present invention relates to an adult stem cell line introduced with an HGF gene and a neurogenic transcription factor gene of a bHLH family, a preparation method of the adult stem cell line, and a method for treating neurological diseases comprising the step of transplanting the adult stem cell line to a subject having neurological diseases. The adult stem cells according to the present invention, which are introduced with an HGF gene and a neurogenic transcription factor gene of a bHLH family, can be used to treat chronic impairment caused by cell death following stroke. Thus, the adult stem cells can be developed as a novel therapeutic agent or widely used in clinical trial and research for cell replacement therapy and gene therapy that are applicable to neurological diseases including Parkinson's disease, Alzheimer disease, and spinal cord injury as well as stroke. 1. A modified mesenchymal stem cell , comprising a mesenchymal stem cell having introduced therein:a gene encoding a hepatocyte growth factor (HGF); anda gene encoding neurogenin 1.2. The modified mesenchymal stem cell of claim 1 , wherein the mesenchymal stem cell is derived from one or more tissues selected from the group consisting of bone marrow claim 1 , blood claim 1 , umbilical cord blood claim 1 , umbilical cord claim 1 , adipose tissue claim 1 , liver claim 1 , skin claim 1 , gastrointestinal tract claim 1 , muscle claim 1 , placenta and uterus claim 1 , adult bone marrow claim 1 , adult blood claim 1 , adult adipose tissue claim 1 , liver claim 1 , skin claim 1 , gastrointestinal tract claim 1 , muscle claim 1 , placenta and uterus.3. The modified mesenchymal stem cell of claim 1 , wherein the mesenchymal stem cell is derived from bone marrow.4. The modified mesenchymal stem cell of claim 1 , wherein:the gene encoding HGF comprises a nucleic acid sequence of SEQ ID NO 1;{'b': 1', '1', '2, 'the gene encoding neurogenin 1 comprises a nucleic acid sequence of SEQ ID NO 2; or the gene ...

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24-01-2019 дата публикации

CELL PREPARATION METHOD

Номер: US20190024054A1

Provided is a method of preparing a somatic cell including converting a differentiated somatic cell of a mammal to other somatic cell by culturing the differentiated somatic cell in a medium for inducing differentiation of the somatic cell other than the differentiated somatic cell in the presence of a TGF-β pathway inhibitor. 1. A method of generating a somatic cell comprising converting a differentiated somatic cell of a mammal to other somatic cell by culturing the differentiated somatic cell in a medium for inducing a somatic cell other than the aforementioned differentiated somatic cell in the presence of a TGF-β pathway inhibitor.2. The method according to claim 1 , wherein the TGF-β pathway inhibitor is a D4476 claim 1 , SB431542 claim 1 , LY2157299 claim 1 , SD208 or ALK5 inhibitor II.3. The method according to claim 1 , wherein the TGF-β pathway inhibitor is an ALK5 inhibitor II.4. The method according to claim 1 , wherein the fibroblast is converted to a mesenchymal cell.5. The method according to claim 1 , wherein the fibroblast or keratinocyte is converted to an osteoblast.6. The method according to claim 1 , wherein the fibroblast or peripheral blood mononuclear cell is converted to a white adipocyte.7. The method according to claim 1 , wherein the fibroblast or keratinocyte is converted to a brown adipocyte.8. The method according to claim 6 , wherein the medium for inducing differentiation of the somatic cell comprises a Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) agonist.9. The method according to claim 1 , wherein the fibroblast is converted to a chondrocyte.10. The method according to claim 1 , wherein the fibroblast is converted to a myoblast.11. The method according to claim 1 , wherein the fibroblast is converted to a Schwann cell.12. The method according to claim 1 , wherein the keratinocyte is converted to a urothelial cell.13. The method according to claim 1 , wherein the fibroblast is converted to a mesenchymal stem cell.1415-. ( ...

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24-04-2014 дата публикации

ENHANCED MSC PREPARATIONS

Номер: US20140112893A1
Принадлежит: MESOBLAST INTERNATIONAL SARL

The present invention provides preparations of MSCs with important therapeutic potential. The MSC cells are non-primary cells with an antigen profile comprising less than about 1.25% CD45+ cells (or less than about 0.75% CD45+), at least about 95% CD105+ cells, and at least about 95% CD166+ cells. Optionally, MSCs of the present preparations are isogenic and can be expanded ex vivo and cryopreserved and thawed, yet maintain a stable and uniform phenotype. Methods are taught here of expanding these MSCs to produce a clinical scale therapeutic preparations and medical uses thereof. 1. A mesenchymal stem cell (MSC) preparation comprising:a. at least about 1 billion human bone marrow-derived MSCs; and i. less than about 0.75% CD45+ cells;', 'ii. at least about 95% CD105+ cells; and', 'iii. at least about 95% CD166+ cells., 'b. an antigen profile comprising2. The MSC preparation of claim 1 , wherein the at least about 1 billion human bone marrow-derived MSCs are isogenic.3. The MSC preparation claim 2 , wherein the MSC preparation comprises at least about 20 billion human bone marrow-derived MSCs in number.4. The MSC preparation claim 1 , wherein the MSCs express at least about 13 pg to about 44 pg TNFRI per million MSCs and optionally wherein the MSCs claim 1 , when mixed with peripheral blood mononuclear cells (PBMCs) at a ratio of about 5 PBMCs per MSC claim 1 , are capable of inhibiting IL2Rα expression by CD3/CD28-activated PBMCs cells by at least about 30% claim 1 , relative to a control.5. The MSC preparation of claim 4 , wherein the MSCs are isogenic and are at least 4.5×10human bone marrow-derived MSCs in number.6. The MSC preparation of claim 5 , further comprising a cryopreservative.7. The MSC preparation of claim 6 , wherein after a freeze-thaw cycle claim 6 , at least about 70% of the MCSs are viable claim 6 , as assessed by dye exclusion.8. The MSC preparation of claim 5 , wherein the MSCs:a. are capable of at least 1 population doubling; andb. retain said ...

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04-02-2016 дата публикации

THEOBROMINE COMPOSITIONS USEFUL FOR INCREASING FETAL WEIGHT GAIN AND ENHANCING BONE PROPERTIES

Номер: US20160030434A1
Принадлежит:

Compositions and methods for culturing cells with theobromine are provided, as well as cells derived thereby. Theobromine compositions for enhancing bone formation, increasing bone density, increasing interconnections of internal bone, increasing bone mass, treating cartilage and/or bone defects, increasing fetal birth weight, preventing tooth decay, remineralizing a tooth surface, treating dentine hypersensitivity, and application to a bone site to promote new bone growth at the site are also provided. 1. An isolated cell in a culture medium , said culture medium comprising theobromine , a salt or double salt of theobromine , or a co-crystal comprising theobromine.2. The isolated cell of claim 1 , wherein said isolated cell is a mammalian cell.3. The isolated cell of claim 1 , wherein said isolated cell is a stem cell.4. The stem cell of claim 3 , wherein said stem cell is a mesenchymal stem cell.5. The cell of claim 1 , wherein said theobromine claim 1 , salt or double salt of theobromine claim 1 , or co-crystal comprising theobromine is from 1 to 300 μM.6. A method of culturing a cell claim 1 , the method comprising:culturing said cell in a culture medium, wherein said culture medium comprises theobromine, a salt or double salt of theobromine, or a co-crystal comprising theobromine.7. The method of claim 6 , wherein said cell is a mammalian cell.8. The method of claim 6 , wherein said cell is a stem cell.9. The method of claim 8 , wherein said stem cell is a mesenchymal stem cell.10. The method of claim 6 , wherein said theobromine is from 1 to 300 μM.11. A culture medium comprising theobromine claim 6 , a salt or double salt of theobromine claim 6 , or a co-crystal comprising theobromine.12. The culture medium of claim 11 , wherein said theobromine claim 11 , salt or double salt of theobromine claim 11 , or co-crystal comprising theobromine is from 1 to 300 μM.13. The culture medium of claim 11 , wherein said theobromine claim 11 , salt or double salt of ...

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29-01-2015 дата публикации

METHOD OF MAKING A HYDROGEL

Номер: US20150030681A1
Принадлежит: THE UNIVERSITY OF MANCHESTER

The present invention relates to a novel protocol for making a hydrogel, which shows increased stability compared to hydrogels of the art, and can be reliably reproduced. The hydrogels produced by the methods of the present invention are preferably three dimensional, and particularly suitable for the culture of stem cells. 149-. (canceled)50. A method of making a hydrogel , comprising the steps of:1) providing a peptide solution, wherein the peptide comprises an amphiphilic portion;2) altering a characteristic of the peptide solution, wherein the characteristic is ionic strength, pH, temperature, or ion concentration, to form an optically transparent first solution;3) maintaining the solution of 2) under conditions suitable for the formation of a hydrogel;4) liquefying the hydrogel of 3), preferably by mechanical agitation;5) combining the liquefied hydrogel of 4) with i) cells and optionally ii) media to form a second solution and optionally determining the optical transparency of the second solution, to assess its capability of forming a hydrogel; and6) maintaining the second solution of 5) under conditions suitable for the formation of a hydrogel comprising cells encapsulated therein.51. A method of making a hydrogel according to claim 50 , wherein the characteristic of step 2) to be altered is the pH claim 50 , wherein preferably the alteration comprises increasing the pH to between 8 and 10 claim 50 , preferably to between 9 and 9.5 claim 50 , preferably to form a homogenous first liquid claim 50 , preferably at a temperature between 60° C. and 95° C.52. A method of making a hydrogel according to claim 50 , wherein step 1) and/or 2) further comprises the step of adding a buffer solution to either the peptide solution or first solution claim 50 , preferably wherein where the buffer is added to the first solution it is added at a ratio of 1 part buffer to between 2 and 8 parts first solution; and preferably wherein the buffer may be selected from the group ...

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02-02-2017 дата публикации

GLUCOMANNAN SCAFFOLDING FOR THREE-DIMENSIONAL TISSUE CULTURE AND ENGINEERING

Номер: US20170029764A1
Автор: Lee C. Chang I.
Принадлежит:

The present invention provides a neutralized glucomannan scaffold capable of promoting cell growth and suitable for three-dimensional tissue culture and engineering. The present invention also provides methods for making and degrading the neutralized glucomannan scaffold. The present invention further provides a method of growing cells on a neutralized glucomannan scaffold. 1. A method of preparing a neutralized glucomannan scaffold , the method comprising contacting a basic glucomannan scaffold having a pH of greater than about 8 with an aqueous solution under vacuum pressure , wherein the aqueous solution is selected from the group consisting of a buffered solution , an acidic solution and a cell culture medium , to form a neutralized glucomannan scaffold having a pH of about 7 , thereby preparing the neutralized glucomannan scaffold.2. The method of claim 1 , wherein the contacting is performed at a temperature of from about 0° C. to about 130° C.3. The method of claim 1 , wherein the contacting is performed at a temperature of from about 20° C. to about 50° C.4. The method of claim 1 , wherein the contacting is performed at a temperature of about 37° C.5. The method of claim 1 , wherein the contacting is performed at a pressure of from about 0.1 mmHg to about 760 mmHg.6. The method of claim 1 , wherein the contacting is performed for a period of from about 1 minute to about 1 month.7. The method of claim 1 , wherein the contacting is performed for a period of from about 1 hour to about 1 week.8. The method of claim 1 , wherein the contacting is performed for a period of from about 1 hour to about 1 day.9. The method of claim 1 , wherein the contacting is performed for a period of from about 8 to about 20 hours.10. The method of claim 1 , wherein the basic glucomannan scaffold further comprises a cell adhesion promoter.11. The method of claim 10 , wherein the cell adhesion promoter is selected from the group consisting of poly-L-lysine (PLL) claim 10 , poly-D- ...

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04-02-2016 дата публикации

COMPOSITIONS AND METHODS FOR OBTAINING ENRICHED MESENCHYMAL STEM CELL CULTURES

Номер: US20160032248A1
Принадлежит: StemCell Technologies, Inc.

The disclosure provides a method of culturing cells of the mesenchymal cell lineage, said method comprising contacting the cells with a culture media comprising a CSF1R kinase inhibitor. The disclosure also provides a method of culturing cells from bone marrow and/or compact bone to enrich the cells with cells of the mesenchymal cell lineage comprising contacting the cells with a culture media comprising a CSF1R kinase inhibitor. Cell culture media comprising a CSF1R kinase inhibitor and useful for culturing cells of the mesenchymal cell lineage and/or enriching cells of the mesenchymal cell lineage is also provided. 1. A method of culturing cells of the mesenchymal cell lineage , said method comprising contacting the cells with a culture media comprising a CSF1R kinase inhibitor.2. The method of claim 1 , wherein the method comprises:a) harvesting cells from a tissue sample obtained from a subject, wherein the harvested cells comprise cells of the mesenchymal cell lineage, andb) contacting the harvested cells with a culture media comprising a CSF1R kinase inhibitor, and optionallyc) obtaining a population of cells enriched for cells of the mesenchymal cell lineage.3. (canceled)4. The method of or claim 1 , wherein the CSF1R kinase inhibitor is GW2580 claim 1 , KI20227 claim 1 , HY-13075 claim 1 , cFMS Receptor Inhibitor II claim 1 , cFMS Receptor Inhibitor III claim 1 , cFMS Receptor Inhibitor IV or ARRY-382.5. The method of claim 2 , wherein the harvested cells further comprise non-mesenchymal cells.67-. (canceled)8. The method of claim 1 , wherein the cells of the mesenchymal cell lineage comprise at least one of a mesenchymal stem cell claim 1 , a mesenchymal cell progenitor and a stromal-derived cell.9. The method of claim 2 , wherein the tissue sample comprises bone marrow claim 2 , compact bone or adipose tissue.10. The method of claim 1 , wherein the cells are contacted with the culture media for at least one hour claim 1 , at least one day or at least one ...

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17-02-2022 дата публикации

PHARMACEUTICAL COMPOSITION FOR TREATING PANCREATITIS, COMPRISING CLONAL STEM CELLS

Номер: US20220047640A1
Принадлежит: SCM LIFESCIENCE CO., LTD.

The present disclosure relates to a composition for preventing, treating, or alleviating pancreatitis, containing monoclonal stem cells obtained by improved subfractionation culturing of stem cells, and to a method for preparing the same. According to the improved method of subfractionation culture and proliferation of stem cells of the present disclosure, it is possible to obtain a large quantity of desired monoclonal stem cells in a short time by rapid proliferation of monoclonal stem cells, and the monoclonal mesenchymal stem cells obtained thereby are stem cells with enhanced therapeutic effects on pancreatitis, and thus can may beneficially used as a pancreatitis therapeutic agent. 1. A pharmaceutical composition for preventing or treating pancreatitis , the pharmaceutical composition comprising monoclonal stem cells obtained by steps of:1) culturing bone marrow isolated from a subject in a first vessel;2) transferring only a supernatant from the first vessel to a new vessel and culturing the supernatant;3) culturing cells present in the new vessel and obtaining a supernatant;4) obtaining monoclonal stem cells by repeating steps 2) and 3) at least once using the supernatant of step 3) as the supernatant of the first vessel of step 2); and{'sup': '2', '#text': '5) inoculating and culturing the monoclonal stem cells of step 4) in a medium at a cell density of 50 to 1,000 cells/cm.'}2. The pharmaceutical composition of claim 1 , wherein the culture of step 5) is performed by inoculating the monoclonal stem cells in a medium at a cell density of 1 claim 1 ,000 cells/cm.3. The pharmaceutical composition of claim 1 , wherein the culture of step 5) is performed at passage 2 to passage 8.4. The pharmaceutical composition of claim 1 , wherein the medium of step 5) is supplemented with an antioxidant.5. The pharmaceutical composition of claim 1 , wherein the pancreatitis is a chronic pancreatitis or an acute pancreatitis.6. The pharmaceutical composition of claim 1 , ...

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31-01-2019 дата публикации

METHOD OF TREATING GRAFT VERSUS HOST DISEASE

Номер: US20190030080A1
Принадлежит: MESOBLAST, INC.

A method for preventing the development of or treating GvHD complications in a mammalian patient which comprises administering to the mammal a population of cells enriched for STRO-1cells and/or progeny thereof and/or soluble factors derived therefrom. 1. A method for preventing the development of or treating GvHD complications in a mammalian patient which comprises administering to the mammal a population of cells enriched for STRO-1cells and/or progeny thereof and/or soluble factors derived therefrom.2. A method according top which comprises administering to the mammal (a) precursors of bone marrow lineage cells claim 1 , and (b) a population of cells enriched for STRO-1cells and/or progeny thereof and/or soluble factors derived therefrom.3. The method according to claim 2 , wherein the population of cells enriched for STRO-1cells and/or progeny cells thereof and/or soluble factors derived therefrom is administered to the mammal prior to administration of the precursors of bone marrow lineage cells.4. The method according to claim 2 , wherein the population of cells enriched for STRO-1cells and/or progeny cells thereof and/or soluble factors derived therefrom is co-administered with the precursors of bone marrow lineage cells.5. The method according to any one of to claim 2 , wherein the precursors of bone marrow lineage cells are allogeneic cells administered to the mammal to treat a malignant or genetic disease of the blood.6. A method according to any one of to wherein the STRO-1cells and/or progeny thereof are allogeneic.7. A method according to any one of to wherein the population of cells enriched for STRO-1cells and/or progeny cells thereof and/or soluble factors derived therefrom is administered systemically.8. The method according to claim 7 , wherein the population of cells enriched for STRO-1cells and/or progeny cells thereof and/or soluble factors derived therefrom is administered by intravenous injection.9. The method of any one of to claim 7 , ...

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04-02-2021 дата публикации

COATED BIOLOGICAL COMPOSITION

Номер: US20210030688A1
Принадлежит:

A coated biological composition has a mixture of biologic material and a volume of a liquid protectant. The mixture of biologic material has non-whole cellular components or whole cells or combinations of the non-whole cellular components and whole cells, wherein the mixture is compatible with biologic function. The volume of a liquid protectant is intermixed with the mixture of biologic material, wherein the liquid protectant forms a coating externally enveloping each of the non-whole cellular components, if any, and each of the whole cells, if any, of the mixture of biologic material, to form the coated biological composition. The coated biological composition is frozen and thereafter thawed and then frozen a second time for storage or frozen at least once and thawed and stored under refrigeration above freezing, or frozen and thawed and then concentrated by drying, or while frozen without thawing lyophilized for ambient or room temperature storage. 1. A method of making a coated biological composition comprises the steps of:collecting, recovering and processing bone marrow from a cadaver donor;mechanically separating cellular and non-cellular components of bone marrow from cadaverous bone;concentrating by centrifugation and filtering;separation by density gradient centrifugation;collecting non-cellular fractions or non-cellular components or combinations thereof of predetermined density;washing the non-cellular fractions or non-cellular components or combinations thereof to create a mixture;quantifying non-whole cell fraction concentration exceeds zero;suspending the mixture to a predetermined concentration in a liquid protectant to coat the mixture and form the coated biological composition;freezing the suspended mixture at a predetermined controlled rate; andthereafter thawing and then freezing a second time for storage or frozen at least once thawed and stored under refrigeration above freezing, or frozen and thawed and then concentrated by drying, or while ...

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31-01-2019 дата публикации

METHOD FOR MANUFACTURING CULTURE PRODUCT LIQUID

Номер: US20190032019A1
Автор: GLADKOV Alexei
Принадлежит:

A method of manufacturing a culture product liquid includes extracting an intermediate-layer bone marrow liquid positioned in an intermediate layer from bone marrow liquid separated in layered fashion and culturing the intermediate-layer bone marrow liquid with a culture liquid. First stem cells are collected from a first culture container when the total area of the first stem cells reaches a first target ratio of the bottom surface area of the first culture container. Second stem cells are cultured together with the culture liquid. The second stem cells are fixed to the bottom surface of a second culture container, and a culture product liquid including a predetermined metabolite secreted from a single type of second stem cells grown from the second culture container is extracted when the total area of the second stem cells reaches a second target ratio of the bottom-surface area of the second culture container. 1. A method for manufacturing a culture product liquid , using a stem cell made from a bone marrow liquid collected from a donor , the method comprising the steps of:separating a bone marrow liquid for separating in layers a bone marrow liquid collected from a donor;extracting a bone marrow liquid for extracting an intermediate-layer bone marrow liquid positioned in an intermediate layer of the bone marrow liquid separated in layers by the step of separating a bone marrow liquid;first fixing a stem cell for feeding the intermediate-layer bone marrow liquid extracted by the step of extracting a bone marrow liquid and a predetermined culture liquid into a first culture container having a predetermined capacity and a bottom surface of a predetermined area, allowing the first culture container to statically stand for a predetermined period of time, and fixing a first stem cell contained in the intermediate-layer bone marrow liquid to a bottom surface of the first culture container;first culturing a stem cell for discharging the culture liquid in the first ...

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08-02-2018 дата публикации

GENETICALLY MODIFIED MESENCHYMAL STEM CELL EXPRESSING KLOTHO

Номер: US20180037868A1
Принадлежит:

A genetically modified mesenchymal stem cell (MSC) includes an exogenous nucleic acid that includes a Klotho encoding region operably linked to a promoter or promoter/enhancer combination. The MSCs can be used for the treatment of cancer, organ fibrosis, renal failure, age-related changes of organs or organ systems, arteriosclerosis, and neurodegenerative diseases, such as Alzheimer's disease (AD), Multiple sclerosis (MS), Huntington's disease, Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease, and Schizophrenia, as well as dementia, diabetes mellitus, sepsis and autoimmune diseases and autoimmune-related diseases. 1. A genetically modified mesenchymal stem cell comprising an exogenous nucleic acid comprising a Klotho-encoding region operably linked to a promoter or promoter/enhancer combination , wherein the genetically modified mesenchymal stem cell exhibits increased Klotho expression compared to an unmodified mesenchymal stem cell.2. The genetically modified cell according to claim 1 , wherein the exogenous nucleic acid is comprised in a viral vector.3. The genetically modified cell according to claim 1 , wherein the promoter is a constitutive promoter.4. The genetically modified cell according to claim 1 , wherein the constitutive promoter is the EFS claim 1 , PGK or EF1alpha promoter.59.-. (canceled)10. The genetically modified cell according to claim 1 , wherein the Klotho encoding region encodes a protein according to one of SEQ ID NO 6 to 10 claim 1 , or wherein the Klotho encoding region comprises or consists of a sequence according to SEQ ID NO 1 to 5.11. The genetically modified cell according to claim 1 , wherein the Klotho encoding region encodes for a secreted form of the Klotho protein.12. (canceled)13. The genetically modified cell according to claim 1 , wherein the secreted form the Klotho protein possess an amino acid sequence with an identity of at least 80% to SEQ ID NO 8 claim 1 , or an amino acid sequence according to SEQ ID NO 8.14. ( ...

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06-02-2020 дата публикации

Prevention and treatment of bone and cartilage damage or disease

Номер: US20200038449A1
Принадлежит: Xintela AB

Compositions and methods for the prevention and/or treatment of conditions involving disease or damage in mammalian cartilage and bone, using mesenchymal stem cells isolated with anti-integrin α10 antibodies are disclosed. 169.-. (canceled)70. An enriched integrin α10population of Mesenchymal Stem Cells (MSC) , wherein at least 60% of the cells of the population of MSCs express integrin α10 subunit , wherein the MSCs are MHCII negative and CD45 negative , and wherein said MSC is selected from a mesenchymal stem cell , a mesenchymal progenitor cell , and a mesenchymal stromal cell.71. The enriched integrin α10population of claim 70 , wherein at least 65% claim 70 , at least 70% claim 70 , at least 75% claim 70 , at least 80% claim 70 , at least 85% claim 70 , at least 90% claim 70 , at least 95% claim 70 , at least 96% claim 70 , at least 97% claim 70 , at least 98% claim 70 , at least 99% claim 70 , or 100% of the total cells comprised in the population express integrin α10 subunit.72. The enriched integrin α10population of claim 70 , wherein said population is an in vitro cell culture.73. The enriched integrin α10population of claim 70 , wherein the cells that express integrin α10 are isolated with an anti-integrin α10 antibody.74. The enriched integrin α10population of claim 73 , wherein the anti-integrin α10 antibody is a monoclonal antibody.75. The enriched integrin α10population of claim 70 , wherein the cells are derived from adipose tissue claim 70 , bone marrow claim 70 , synovial membrane claim 70 , peripheral blood claim 70 , cord blood claim 70 , umbilical cord blood claim 70 , Wharton's jelly claim 70 , or amniotic fluid.76. The enriched integrin α10population of claim 70 , wherein the MSCs express CD44 claim 70 , CD90 and CD105.77. A method of promoting or inducing fracture healing in a subject in need thereof claim 70 , said method comprising administering a therapeutically effective amount of the enriched integrin α10population of MSCs of to the ...

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06-02-2020 дата публикации

Tissue repair by stem cell recruitment and differentiation

Номер: US20200038450A1
Автор: Chang Hun Lee
Принадлежит: Columbia University of New York

Provided herein are compositions and methods for healing cartilage tissue defects or injury by forming fibrochondrocyte cells or fibrochondrocyte-like cells from recruited progenitor cells, such as mesenchymal stem cells.

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24-02-2022 дата публикации

METHOD FOR PRODUCING A VIRUS-FREE PLATELET LYSATE MATERIAL

Номер: US20220056414A1
Принадлежит: PL BIOSCIENCE GMBH

The invention relates to a method for producing a material for preparing a substrate for cultivating living cells. The invention further relates to a platelet lysate material and its use.The solution of the problem underlying the invention is based on the combination of at least two different treatments with different virus inactivation procedures.Combining two or more procedures for inactivation of virus particles and/or virus components ensures that a wide range of viruses (e.g. enveloped and non-enveloped viruses) are inactivated so as to provide a safe product for clinical and pharmaceutical applications. Moreover, a platelet lysate material comprising blood platelet lysate is provided, wherein the material is a liquid or dry material that is essentially devoid of vims particles and/or virus components. 1. A method for producing a material for preparing a substrate for cultivating living cells , said method comprising:Providing a blood platelet lysate, andExposing said platelet lysate to at least two different treatments, each treatment being capable of inactivating virus particles and/or virus components, so as to provide a virus-free or at least virus-reduced platelet lysate material.2. The method according to claim 1 , wherein the treatments comprise at least two different treatments selected from the group consisting of pasteurization claim 1 , dry heat claim 1 , vapor heat claim 1 , irradiation with ultraviolet light claim 1 , irradiation with gamma rays claim 1 , irradiation with X-rays claim 1 , electron-beam irradiation claim 1 , nano-filtration claim 1 , and solvent/detergent treatment.3. The method according to claim 1 , wherein said blood platelet lysate is liquid claim 1 , said liquid platelet lysate being exposed to the treatments.4. The method according to claim 1 , wherein said blood platelet lysate is dried before the treatments claim 1 , so as to provide a dry platelet lysate material claim 1 , said dry platelet lysate material being exposed to ...

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07-02-2019 дата публикации

GENETIC MODIFIED PLURI- OR MULTIPOTENT STEM CELLS AND USES THEREOF

Номер: US20190040134A1
Автор: EHNINGER Armin
Принадлежит: GEMoaB Monoclonals GmbH

The invention concerns pluri- or multipotent stem cells (SCs), e.g. human pluri- or multipotent stem cells (hSCs) engineered to express a multispecific antibody and which further express, on their surface, a human immune cell co-stimulatory ligand or an active fragment thereof. 114.-. (canceled)15. A mesenchymal stem cell (MSC) engineered to express a bispecific antibody capable of specifically binding to CD33 and CD3.16. The MSC of claim 15 , wherein said bispecific antibody is a single chain bispecific antibody.17. The MSC of claim 15 , wherein said bispecific antibody is a humanized bispecific antibody.18. The MSC of claim 15 , wherein said bispecific antibody comprises a linker.19. The MSC of claim 18 , wherein said linker is a GS linker.20. The MSC of claim 15 , wherein said bispecific antibody comprises a variable light (VL) antibody domain and variable heavy (VH) antibody domain that specifically bind to CD33 (CD33 VL and CD33 VH).21. The MSC of claim 20 , wherein said CD33 VH comprises a VH CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 3 and 9-12 claim 20 , a VH CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4 and 13-16 claim 20 , and a VH CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 5 claim 20 , 17-20; and wherein said CD33 VL comprises a VL CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 6 and 21-24 claim 20 , a VL CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 7 and 25-28 claim 20 , and a VL CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 8 and 29-32.22. The MSC of claim 20 , wherein said CD33 VH comprises a VH CDR1 comprising SEQ ID NO: 3 claim 20 , a VH CDR2 comprising SEQ ID NO: 4 claim 20 , and a VH CDR3 comprising SEQ ID NO: 5; and said CD33 VL comprises a VL CDR1 comprising SEQ ID NO: 6 claim 20 , a ...

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15-02-2018 дата публикации

USE OF MESENCHYMAL STEM CELLS IN TREATING OSTEOARTHRITIS

Номер: US20180042966A1
Автор: Hung Shih-Chieh
Принадлежит:

The present invention relates to a use of hypoxia-cultured mesenchymal stem cells (MSCs) for manufacture of a cell graft for treating a musculoskeletal disorder, particularly osteoarthritis. 121-. (canceled)22. A method of treating a musculoskeletal disorder , comprising:administering a cell graft comprising hypoxic mesenchymal stem cells (MSCs) to a patient in need thereof.23. The method of claim 22 , wherein the musculoskeletal disorder is selected from the group consisting of sprains; strains and tears of ligaments claim 22 , tendons claim 22 , muscles and cartilage; tendonitis; tenosynovitis; fibromyalgia; osteoarthritis; rheumatoid arthritis; polymyalgia rheumatic; bursitis; acute and chronic back pain; osteoporosis; carpal tunnel syndrome; DeQuervains's disease; trigger finger; tennis elbow; rotator cuff; ganglion cysts; osteogenesis imperfecta; and Duschennes claim 22 , Hurler's and Hunter's syndromes.24. The method of claim 22 , wherein the musculoskeletal disorder is osteoarthritis.25. The method of claim 22 , wherein the cell graft is administered through direct implantation claim 22 , intravenous injection claim 22 , intramuscular injection claim 22 , intraosseous injection claim 22 , intraperitoneal injection claim 22 , intradermal injection claim 22 , subcutaneous injection claim 22 , or intra-articular injection.26. The method of claim 25 , wherein the cell graft is administered through intra-articular injection.27. The use of claim 25 , wherein the cell graft is administered through direct implantation.28. The method of claim 22 , wherein the cell graft further comprises an injectable vehicle.29. The method of claim 28 , wherein the injectable vehicle is at least one selected from the group consisting of a bio-polymer claim 28 , a biomimetic composite of nature polymers and a synthetic polymer.30. The method of claim 29 , wherein the biomimetic composite of nature polymers is hyaluronic acid claim 29 , collagen claim 29 , fibronectin claim 29 , ...

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15-02-2018 дата публикации

METHOD FOR REDUCING THE INFLAMMATORY ACTIVITY OF A STEM CELL TRANSPLANT AND USE THEREOF

Номер: US20180042967A1
Принадлежит: Neuroplast Beheer B.V.

The disclosure is in the field of cell therapy, more in particular, stem cell transplantation therapy. The disclosure provides methods and compositions for improving the efficacy of stem cell transplantation therapy by reducing the inflammatory activity of a stem cell transplant. More in particular, the disclosure provides a method for preparing a stem cell transplant with reduced inflammatory activity comprising a step of suspending a composition comprising stem cells in a fibrinogen-depleted plasma and/or in a fibrinogen and C-reactive protein-depleted plasma. 17.-. (canceled)8. A composition comprising a hematopoietic stem cell and plasma or serum depleted of fibrinogen and C-reactive protein.9. The composition of claim 8 , additionally depleted of pro-inflammatory cells.10. The composition of claim 8 , wherein the composition comprises a human hematopoietic stem.11. A method of treating a subject claim 8 , the method comprising administering to the subject the composition of .12. The method according to claim 8 , wherein administering to the subject the composition of comprises treating the subject so as to induce tissue regeneration selected from the group consisting of neural claim 8 , vascular and hematopoietic tissue regeneration.13. The method according to claim 12 , wherein the tissue regeneration is a therapy for spinal cord injury.14. The method according to claim 12 , wherein the administration comprises autologous transplantation therapy. This application is a divisional of U.S. patent application Ser. No. 15/029,206, filed Apr. 13, 2016, pending, which is a national phase entry under 35 U.S.C. §371 of International Patent Application PCT/EP2014/072911, filed Oct. 24, 2014, designating the United States of America and published in English as International Patent Publication WO 2015/059300 A1 on Apr. 30, 2015, which claims the benefit under Article 8 of the Patent Cooperation Treaty to European Patent Application Serial No. 13190120.9, filed Oct. 24, ...

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16-02-2017 дата публикации

SELECTION AND USE OF STEM CELLS

Номер: US20170044497A1
Принадлежит: NATIONAL UNIVERSITY OF IRELAND, GALWAY

A population of human stem cells is, or is selected to be, positive for CD271 and acetylated tubulin. Cells are isolated by a method comprising isolation of a cell from a mixed population of cells based on expression of cell surface markers, wherein the markers are CD271 and acetylated tubulin. The isolated cells may be used in therapy for example by producing tissues such as bone, cartilage or tendon, or in pharmaceutical compositions comprising isolated cells. 1. A population of human stem cells selected to be positive for CD271 and acetylated tubulin.2. The population of cells of claim 1 , wherein 30% or more of the cells are positive for both CD271 and acetylated tubulin.3. The population of cells of claim 2 , wherein 50% or more of the cells are positive for both CD271 and acetylated tubulin.4. The population of cells of claim 2 , wherein 70% or more of the cells are positive for both CD271 and acetylated tubulin.5. The population of cells according to of claim 2 , wherein substantially all of the cells are positive for both CD271 and acetylated tubulin.6. Tissue obtained from the population of cells of .7. A method of isolation of a human stem cell claim 2 , comprising isolation of a cell from a mixed population of cells based on expression of cell surface markers claim 2 , wherein the markers are CD271 and acetylated tubulin.8. The method of claim 7 , wherein the mixed population of cells is obtained from a source selected from bone marrow claim 7 , adipose tissue claim 7 , skeletal muscle claim 7 , endometrium claim 7 , placenta claim 7 , umbilical cord blood claim 7 , umbilical cord claim 7 , Wharton's jelly claim 7 , dental pulp and cells derived from pluripotent cells.9. A method of obtaining a clonal population of cells claim 7 , comprising (i) isolating a single cell according to the method of claim 7 , or (ii) providing a single cell positive for CD271 and acetylated tubulin claim 7 , and (iii) deriving a clonal population of cells from the single cell ...

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15-02-2018 дата публикации

METHODS FOR GROWING CELLS

Номер: US20180044637A1
Принадлежит: CHILDREN'S HOSPITAL MEDICAL CENTER

Some embodiments of the invention include methods for growing stem cells comprising growing the stem cells in a cell medium. In certain embodiments, the cell medium has a pH of from about 6.6 to about 7.2. Other embodiments of the invention embodiments include methods for transplanting comprising (a) growing first stem cells in a cell medium having a pH of from about 6.6 to about 7.2, to provide second stem cells and (b) transplanting the second stem cells into a recipient. Other embodiments include the methods where the stem cells that are human stem cells, mouse stem cells, rat stem cells, primate stem cells, or mammalian stem cells. Still other embodiments include growing stem cells in a cell medium having a pH of from about 6.6 to about 7.2 (e.g., from about 6.8 to about 7.0 or about 6.9) that results in modulation of one or more cell properties (e.g., decreased number of cells in the S phase, decreased amount of ROS, etc.) when that property is compared to that of stems cells grown at a pH of about 7.4. Additional embodiments of the invention are also discussed herein. 1. A method for growing first stem cells comprisinggrowing the first stem cells in a cell medium having a pH of from about 6.6 to about 7.2, andrecovering second stem cells.2. The method of claim 1 , wherein the pH of the cell medium is from about 6.7 to about 7.1.3. The method of claim 1 , wherein the pH of the cell medium is from about 6.8 to about 7.0.4. The method of claim 1 , wherein the pH of the cell medium is about 6.9.5. The method of claim 1 , wherein the first stem cells are grown ex vivo.6. The method of claim 1 , wherein the first stem cells are human stem cells claim 1 , mouse stem cells claim 1 , rat stem cells claim 1 , primate stem cells claim 1 , or mammalian stem cells.7. The method of claim 1 , wherein the first stem cells are somatic stem cells claim 1 , tissue-specific stem cells claim 1 , hematopoietic stem cells (HSC) claim 1 , stem cells that express CD34 claim 1 , ...

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03-03-2022 дата публикации

TREATMENT OF VASCULOPATHY WITH PROSTACYCLIN AND MESENCHYMAL STEM CELLS

Номер: US20220062210A1
Принадлежит: United Therapeutics Corporation

Provided are methods for treating or preventing vasculopathy in a subject in need thereof, comprising administering to the subject a prostacyclin and a mesenchymal stem cell (MSC) or a MSC-conditioned culture medium or administering to the subject a MSC or a MSC-conditioned culture medium that has treated with prostacyclin. Pharmaceutical compositions suitable for such treatments are also provided. 116.-. (canceled)17. A pharmaceutical composition comprising treprostinil or a pharmaceutically acceptable salt or ester thereof and a pharmaceutically effective amount of exosomes and a pharmaceutically acceptable carrier , wherein the exosomes are isolated from a mesenchymal stem cell culture comprising mesenchymal stem cells and treprostinil or a pharmaceutically acceptable salt or ester thereof , wherein the treprostinil or pharmaceutically acceptable salt or ester thereof is present in an amount sufficient to increase the amount of vascular endothelial growth factor contained in the mesenchymal stem cell culture and wherein the exosomes have increased VEGF-A gene transcript levels relative to exosomes obtained from a mesenchymal stem cell culture to which a prostacyclin was not added during culturing.18. The pharmaceutical composition of claim 17 , wherein the amount of the treprostinil or pharmaceutically acceptable salt or ester thereof added to the culture medium is between about 200 μg/mL and about 300 μg/mL.191. The pharmaceutical composition of claim claim 17 , wherein the mesenchymal stem cell is obtained from bone marrow.201. The pharmaceutical composition of claim claim 17 , wherein the mesenchymal stem cell is a mesenchymal precursor cell.211. The pharmaceutical composition of claim claim 17 , wherein the exosomes have at least about 4-fold increased VEGF-A gene transcript levels relative to exosomes obtained from a mesenchymal stem cell culture to which a prostacyclin was not added during culturing.221. The pharmaceutical composition of claim claim 17 , ...

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03-03-2022 дата публикации

PHARMACEUTICAL COMPOSITION CONTAINING PROTEIN KINASE C ACTIVATOR-TREATED STEM CELLS OR CULTURE THEREOF FOR PREVENTING OR TREATING AUTOIMMUNE DISEASES

Номер: US20220062345A1
Принадлежит: CORESTEM CO.,LTD.

The present invention relates to a pharmaceutical composition for preventing or treating an autoimmune disease, including stem cells treated with a protein kinase C activator or a culture thereof, and more specifically, the present invention relates to a pharmaceutical composition for preventing or treating an autoimmune disease, which can inhibit the function of B cells and have an excellent prophylactic or therapeutic effect for an autoimmune disease. 1. A pharmaceutical composition for preventing or treating an autoimmune disease , comprising stem cells treated with a protein kinase C activator or a culture thereof.2. The pharmaceutical composition of claim 1 , wherein the protein kinase C activator comprises one or more selected from the group consisting of phorbol myristate acetate claim 1 , ingenol 3-angelate claim 1 , bryostatin-1 claim 1 , phorbol-12 claim 1 ,13-dibutyrate claim 1 , prostatin claim 1 , N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide claim 1 , and 5-chloro-N-heptylnaphthalene-1-sulfonamide.3. The pharmaceutical composition of claim 1 , wherein the stem cells are adult stem cells claim 1 , pluripotent stem cells claim 1 , induced pluripotent stem cells claim 1 , or embryonic stem cells.4. The pharmaceutical composition of claim 1 , wherein the adult stem cells are mesenchymal stem cells claim 1 , mesenchymal stromal cells claim 1 , or multipotent stem cells.5. The pharmaceutical composition of claim 1 , wherein the protein kinase C activator increases the expression of CXCL10 in stem cells.6. The pharmaceutical composition of claim 1 , wherein the protein kinase C activator increases apoptosis of B cells by increasing the expression of programmed death-ligand 1 (PD-L1) in stem cells.7. The pharmaceutical composition of claim 1 , wherein the autoimmune disease is selected from the group consisting of lupus (systemic lupus erythematosus) claim 1 , rheumatoid arthritis claim 1 , progressive systemic sclerosis (scleroderma) claim 1 , atopic ...

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19-02-2015 дата публикации

Process for Ex Vivo Expansion of Stem Cells in a Bioreactor

Номер: US20150050730A1
Принадлежит:

The present invention refers to a process of ex vivo expansion of stem cells, in a bioreactor, in particular hematopoietic stem/progenitor cells co-cultured with mesenchymal stem cells immobilized on microcarriers, for transplantation. The process comprises the steps of: a) forming a suspension of mesenchymal stem cells immobilized on microcarriers, b) inoculating in a bioreactor containing an expansion medium, hematopoietic cells co-cultured with mesenchymal stem cells immobilized on microcarriers c) expansion of hematopoietic cells. The process of the invention is capable of being implemented in a Kit. 1. Process for rapid expansion of number of hematopoietic stem and progenitor cells , characterized in that it comprises simultaneously:a) providing a bioreactor system under stirred dynamic conditions;b) providing a co-culture of hematopoietic stem cells with mesenchymal stem cells on inert supports, in the presence of growth factors in serum free medium, constituting a cell culture;c) maintaining the cell culture in said bioreactor under dynamic conditions such that the expansion of hematopoietic stem cells is at least 5-fold in less than 20 days.2. Process according to characterized in that it comprises mesenchymal stem cells isolated from bone marrow or umbilical cord blood claim 1 , or from umbilical cord matrix or adipose tissue or amniotic fluid claim 1 , or urine.3. Process according to characterized in that it comprises mesenchymal stem cells frozen or fresh immobilized on inert supports.4. Process according to characterized in that it comprises hematopoietic stem/progenitor cells isolated from umbilical cord blood claim 1 , bone marrow claim 1 , mobilized peripheral blood and fetal liver.5. Process according to characterized in that it comprises mesenchymal stem cells of human origin.6. Process according to characterized in that it comprises mesenchymal stem cells and hematopoietic stem cells from the same donor.7. Process according to claim 1 , ...

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14-02-2019 дата публикации

METHODS OF TREATING OR PREVENTING RESPIRATORY CONDITIONS

Номер: US20190046575A1
Принадлежит: MESOBLAST, INC.

The present disclosure provides methods of treating or preventing respiratory condition and/or for treating an IgE-mediated allergy and/or for reducing an allergic response to an allergen and/or for inducing anergy to an allergen in a subject and/or improving lung function in a subject suffering from an allergy comprising administering to a subject a population of cells enriched for STRO-1 cells and/or progeny thereof and/or soluble factors derived therefrom. 1. A method of treating a respiratory condition in a human subject , the method comprising administering to the subject a population of cells enriched for STRO-1 mesenchymal precursor cells or progeny thereof.2. The method of claim 1 , wherein the respiratory condition is an acute respiratory condition or a chronic respiratory condition.3. The method of claim 1 , wherein the respiratory condition is an inflammatory respiratory condition claim 1 , an obstructive respiratory condition or a restrictive respiratory condition.4. The method of claim 3 , wherein the respiratory condition is an obstructive respiratory condition or allergy or an inflammatory lung condition.5. The method of claim 4 , wherein the respiratory condition is asthma.6. The method of claim 5 , wherein the asthma is acute asthma claim 5 , chronic asthma claim 5 , severe asthma and/or refractory asthma.7. The method of claim 6 , wherein the asthma is long acting beta agonist (LABA) refractory asthma or steroid refractory asthma.8. The method of claim 3 , wherein the respiratory condition is a restrictive respiratory condition.9. The method of claim 8 , wherein the respiratory condition is idiopathic pulmonary fibrosis.10. The method of claim 1 , wherein the condition is allergy to house dust mite allergen (HDM) or the allergen is HDM.11. (canceled)12. The method of claim 1 , wherein the population is administered systemically.13. The method of claim 12 , wherein the population is administered intravenously or intranasally.14. The method of claim ...

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13-02-2020 дата публикации

Cell cryopreservation composition and cryopreservation method

Номер: US20200045955A1
Принадлежит: Osaka University NUC, Saraya Co Ltd

This composition can be easily added when cryopreserving cells and improves cell viability. 1 volume % of the composition containing 0.01 wt % to 20 wt % of a sophorose lipid is added just before or up to 6 hours before cryopreservation and cells are stored. This composition can improve cryopreservation cell viability as it reduces freezing damage to cells. With this composition, cells can be stored without using DMSO and blood serum. This is a simple and inexpensive storage method as it does not require fine control of the freezing rate during cell cryopreservation.

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13-02-2020 дата публикации

SYNTHETIC NICHE MATRICES FOR STEM CELL CULTURE

Номер: US20200046881A1
Принадлежит:

The present invention relates to a supermatrix of synthetic niches comprising at least two matrices of niches wherein each matrix comprises n×m niches and wherein the distance (d) between a matrix and the other is greater than zero and wherein in each matrix every synthetic niche has one or more walls in common with the others synthetic niches of the matrix. 1. A supermatrix of synthetic niches comprising at least two matrices of synthetic niches ,wherein each matrix comprises n×m synthetic niches, wherein n and m, the same or different from each other, independently have a value ≥1, provided that one of m or n is ≥2 and with a maximum value of m and n which allows to maintain the structure of the single synthetic niche intact such that shrinking of the material does not cause significant disruptions, andwherein the distance (d) between a synthetic niche matrix and the other is greater than zero andwherein in each matrix every synthetic niche has one or more walls in common with the other(s) synthetic niche(s) of the matrix.2. The supermatrix of synthetic niches of claim 1 , wherein said maximum value for n and m is 100.3. The supermatrix of synthetic niches of claim 1 , wherein m and n have the same value.4. The supermatrix of synthetic niches of wherein the height of the supermatrix of synthetic niches is comprised between about 30 and about 100 μm.5. The supermatrix of synthetic niches of claim 1 , comprising or made of a photopolymerizable resin.6. The supermatrix of synthetic niches of claim 1 , wherein the walls of one or more of said synthetic niches are covered with molecules providing a signal inducing maintenance of the pluripotency and/or with molecules facilitating adhesion of cells to the niche.7. A support for the culture of cells comprising claim 1 , or providing support for claim 1 , at least one supermatrix of synthetic niches of claim 1 ,wherein optionally the support has areas not supporting the at least one supermatrix of synthetic niches, and ...

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14-02-2019 дата публикации

Mesenchymal Stem Cells Expressing Biomarkers that Predict the Effectiveness of Mesenchymal Stem Cells for Treating Diseases and Disorders

Номер: US20190048054A1
Принадлежит:

Isolated mesenchymal stem cells, which produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount of at least a first preselected amount, or produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount that does not exceed a second preselected amount, as determined by an assay, such as a RT-PCR assay. Isolated mesenchymal stem cells that produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount of at least the first preselected amount are useful in treating diseases, conditions, and disorders associated with inflammation, while isolated mesenchymal stem cells that produce mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount that does not exceed the second preselected amount are useful in treating bone diseases, conditions, and disorders, including bone injuries. 1. A composition comprising isolated mesenchymal stem cells that produce mRNA encoding tumor necrosis factor-α stimulating gene 6 (TSG-6) protein or a biologically active fragment , derivative , or analogue thereof in an amount of at least a preselected amount , as measured by an assay which comprises:assaying the level of mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof that is produced by a population of isolated mesenchymal stem cells; anddetermining, from the level of mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof produced by said population of isolated mesenchymal stem cells, whether said population of isolated mesenchymal stem cells produces mRNA encoding TSG-6 protein or a biologically active fragment, derivative, or analogue thereof in an amount of said at least preselected amount.2. The composition of wherein said assaying for said levels of mRNA produced by said population of isolated ...

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10-03-2022 дата публикации

COMPOSITIONS AND METHODS OF TREATMENT USING MICROVESICLES FROM BONE MARROW-DERIVED MESENCHYMAL STEM CELLS

Номер: US20220072049A1
Автор: Badiavas Evangelos V.
Принадлежит:

Methods for the treatment of a variety of conditions using microvesicles from bone marrow-derived mesenchymal stem cells are described. 1. A method of treating:(a) a condition selected from the group consisting of epidermolysis bullosa pruriginosa; epidermolysis bullosa acquisita; epidermolysis bullosa dystrophica, pretibial type; epidermolysis bullosa dystrophica, bart type; nonsyndromic congenital nail disorder-8; epidermolysis bullosa dystrophica, with subcorneal cleavage; and transient bullous dermolysis of the newborn in a subject in need thereof comprising administering a therapeutically effective amount of microvesicles, wherein the microvesicles comprise type VII collagen; or(b) Alport syndrome 2, autosomal recessive in a subject in need thereof comprising administering a therapeutically effective amount of microvesicles, wherein the microvesicles comprise type IV collagen; or(c) a condition selected from the group consisting of epidermolysis bullosa simplex with muscular dystrophy; epidermolysis bullosa simplex with pyloric atresia; epidermolysis bullosa, ogna type; epidermolysis bullosa simplex with nail dystrophy; and muscular dystrophy, limb-girdle, autosomal recessive 17 in a subject in need thereof comprising administering a therapeutically effective amount of microvesicles, wherein the microvesicles comprise plectin; or(d) a condition selected from the group consisting of epidermolysis bullosa simplex, autosomal recessive 2 and neuropathy, hereditary sensory and autonomic, 6 in a subject in need thereof comprising administering a therapeutically effective amount of microvesicles, wherein the microvesicles comprise bullous pemphigoid antigen 1; or(e) epidermolytic hyperkeratosis in a subject in need thereof comprising administering a therapeutically effective amount of microvesicles, wherein the microvesicles comprise keratin 1; or(f) benign familial pemphigus in a subject in need thereof comprising administering a therapeutically effective amount of ...

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01-03-2018 дата публикации

METHOD FOR COLLECTING FUNCTIONAL CELLS IN VIVO WITH HIGH EFFICIENCY

Номер: US20180055886A1
Принадлежит:

Biologically low invasive vessels are filled with biological factors that have the activity of mobilizing specific functional cells in the body. The vessels are indwelled in the body. After specific functional cells are mobilized into the vessels, the vessels are removed from the body to collect functional cell populations mobilized to the vessels. Alternatively, the cells are directly collected from the vessels indwelled in the body. 1. A method for collecting bone-marrow-derived stem cells from a subject , wherein the method comprises:(I) implanting for at least 12 hours a vessel that contains a substance of any of (a) to (c) below, completely under the skin in subcutaneous adipose of the subject to induce stem cells present in the bone marrow of the subject to migrate to the vessel implanted in subcutaneous tissue, wherein, as a result of the presence of the substance, stem cells present in bone marrow of the subject enter the vessel implanted in subcutaneous adipose:(a) hyaluronic acid,(b) an extract of a cell or tissue, and(c) a heparin-binding fraction of a cell or tissue extract,wherein the vessel is made from a material that is biologically hypoallergenic when implanted into the subject without any of (a) to (c), and wherein the vessel has one closed end to form an area therein to collect the bone-marrow-derived stem cells; and(II) collecting bone-marrow-derived stem cells from the vessel.2. The method according to claim 1 , wherein the extract of a cell or tissue is an extract of a live skin tissue or blood.3. The method of claim 1 , in which the extract of a cell or tissue is produced by a method comprising the step of immersing a cell or tissue in a solvent.4. The method of claim 1 , in which the heparin-binding fraction of the extract of a cell or tissue is produced by a method comprising the steps of:(a) immersing a cell or tissue in a solvent;(b) contacting immobilized heparin with an extract prepared in step (a); and(c) eluting a heparin-binding ...

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02-03-2017 дата публикации

ENHANCEMENT OF OSTEOGENIC POTENTIAL OF BONE GRAFTS

Номер: US20170056556A1
Принадлежит:

The present invention concerns the enhancement of the osteogenic potential of bone graft by ex vivo treatment with a Wnt polypeptide, such as a liposomal Wnt polypeptide. 158-. (canceled)59. An effective dose of an isolated enhanced mammalian bone graft material comprising enhanced cells wherein the enhanced cells have an increased level of expression for one or more biomarkers comprising Axin2 , Tcf4 , or Lef1 after exposure ex vivo with a liposome comprising a Wnt protein , wherein the increased level of expression for the one or more biomarkers is relative to equivalent cells from isolated mammalian bone graft material unexposed to a liposome comprising a Wnt protein.60. The effective dose of claim 59 , wherein the enhanced cells further have an increased level of expression for one or more biomarkers comprising Runx2 claim 59 , Osterix claim 59 , Osteocalcin claim 59 , or alkaline phosphatase.61. The effective dose of claim 59 , wherein the increased level of expression is increased level of gene expression.62. The effective dose of claim 59 , wherein the increased level of expression is increased level of protein expression.63. The effective dose of claim 59 , wherein the increased level of expression is up to 9× relative to the equivalent cells from isolated mammalian bone graft material.64. The effective dose of claim 59 , wherein the Wnt protein is Wnt3a protein.65. The effective dose of claim 59 , wherein the enhanced cells comprise bone marrow stem cells or bone marrow progenitor cells.66. The effective dose of claim 59 , wherein the enhanced cells comprise mesenchymal stem cells or osteocytes.67. The effective dose of claim 59 , wherein the isolated enhanced mammalian bone graft material comprises enhanced cells with reduced apoptosis after exposure ex vivo with a liposome comprising a Wnt protein claim 59 , wherein the reduced apoptosis is relative to equivalent cells from isolated mammalian bone graft material unexposed to a liposome comprising a Wnt ...

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04-03-2021 дата публикации

INDUCTION MEDIUM AND METHODS FOR STEM CELL CULTURE AND THERAPY

Номер: US20210062140A1
Автор: BETANCOURT Aline
Принадлежит: SANBIO, INC.

Novel MSC stem-cell culture and therapy methods and culture medium compositions for the purpose of inducing, activating, or priming discrete uniform cell phenotypes to selectively promote or suppress inflammation and immunity, yielding polarized, primed, activated, or induced cells used in cell-based therapy. 1. An induction medium comprising:(a) a Toll-like receptor 3 (TLR3) ligand,(b) erythropoietin, and(c) a hypoxia mimetic.2. The induction medium of claim 1 , wherein the TLR3 ligand is poly(I:C).3. The induction medium of claim 2 , wherein the poly(I:C) is present at a concentration of 0.1 picomolar to 100 mM.4. The induction medium of claim 1 , wherein the TLR3 ligand is poly(A:U).5. The induction medium of claim 4 , wherein the poly(A:U) is present at a concentration of 0.1 picomolar to 100 mM.6. The induction medium of claim 1 , further comprising interleukin 4 (IL-4).7. The induction medium of claim 6 , wherein the IL-4 is present at a concentration of 0.1 picomolar to 100 mM.8. The induction medium of claim 1 , further comprising interleukin 13 (IL-13).9. The induction medium of claim 8 , wherein the IL-13 is present at a concentration of 0.1 picomolar to 100 mM.10. The induction medium of claim 1 , wherein the erythropoietin is present at a concentration of 0.5 mU/ml to 50 mU/ml.11. The induction medium of claim 1 , wherein the hypoxia mimetic is cobalt chloride or desferrioxamine.12. The induction medium of claim 11 , wherein the hypoxia mimetic is present at a concentration of 10 μM to 1 mM.13. The induction medium of claim 1 , which does not comprise serum of human or animal origin.14. The induction medium of for use in creating an immunologically polarized mesenchymal stem cell population claim 1 , wherein the immunologically polarized mesenchymal stem cell population possess anti-inflammatory characteristics marked by expression of anti-inflammatory or immunosuppressive mediators.15. A cell culture comprising the induction medium of and a population ...

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28-02-2019 дата публикации

3-D COLLAGEN SCAFFOLD-GENERATED EXOSOMES AND USES THEREOF

Номер: US20190060367A1
Принадлежит: HENRY FORD HEALTH SYSTEM

Described herein is a method for treating and/or ameliorating at least one symptom associated with traumatic brain injury in a subject, the method comprises administering a safe and therapeutically effective amount of a composition comprising exosomes generated from hMSCs in 2D or 3D cultures. 1. A method comprising , administering a safe and therapeutically effective amount of a composition comprising exosomes obtained from an exosome producing cell grown in two-dimensional cell culture or three-dimensional cell culture , to treat a subject suffering from a traumatic brain injury (TBI).2. The method according to claim 1 , wherein the exosome producing cell is a human mesenchymal stem cell.3. The method according to claim 1 , wherein the exosomes are obtained from human mesenchymal stem cells grown in two-dimensional cell culture.4. The method according to claim 1 , wherein the exosomes are obtained from human mesenchymal stem cells grown in three-dimensional cell culture.5. The method according to claim 1 , wherein the three-dimensional cell culture comprises three-dimensional collagen scaffolds.6. The method according to claim 1 , wherein the composition comprises from about 1×10to about 1×10exosomes per kg body weight of the subject.7. The method according to claim 1 , wherein the composition is administered to the subject intravenously claim 1 , subcutaneously claim 1 , cutaneously claim 1 , intraperitoneally claim 1 , intraarterially claim 1 , intracerebrally claim 1 , intrathecally claim 1 , intracerebroventricularly claim 1 , or intranasally.8. The method according to claim 1 , wherein the composition is administered within 24 hours of developing the TBI.9. The method according to claim 1 , wherein treating a subject suffering from a traumatic brain injury comprises treating or preventing one or more symptoms of TBI.10. The method according to claim 9 , wherein one or more symptoms of TBI include one or more of: Difficulty in initiating claim 9 , organizing ...

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09-03-2017 дата публикации

MESENCHYMAL STEM CELLS WITH ENHANCED IMMUNOSUPPRESSIVE CAPABILITY

Номер: US20170065639A1
Автор: HANTASH Basil M.
Принадлежит:

Compositions of HLA-G MSC and methods of using them, including methods of transplanting compositions of HLA-G MSC into human recipients, are provided. Also provided are methods of preparing compositions of HLA-G MSC, including by treatment with DNA methylation inhibitors. 1. A method of generating a composition of HLA-G mesenchymal stem cells (MSCs) , the method comprising:(a) maintaining a population of mammalian tissue-derived MSC for at least two passages in non-differentiating in vitro culture conditions, and(b) contacting the population of mesenchymal stem cells from step (a) with an effective amount of a DNA methylation inhibitor.2. The method of claim 1 , wherein the composition of HLA-G MSCs express HLA-G1 and/or HLA-G3.3. The method of claim 1 , wherein the composition of HLA-G MSCs express HLA-G1 and HLA-G3 and do not express HLA-G5.4. A method of claim 1 , wherein the mammalian tissue-derived MSC is derived from adipose tissue claim 1 , or bone marrow.5. A method of claim 1 , wherein the DNA methylation inhibitor is selected from a group comprising 5-aza-2′-deoxycytidine claim 1 , 5-aza-cytidine claim 1 , 2-pyrimidone-1-β-D-riboside claim 1 , procainamide claim 1 , procaine claim 1 , hydralazine and epigallocatechin-3-gallate.6. A method of claim 1 , wherein the DNA methylation inhibitor is 5-aza-2′-deoxycytidine.7. A method of claim 1 , wherein in step (a) the population of mammalian tissue-derived MSC is maintained in non-differentiating in vitro culture conditions for at least five passages or at least ten passages.8. A method of claim 1 , wherein at least 25% claim 1 , at least 50% claim 1 , or at least 90% of the MSCs in the composition of HLA-G MSCs express HLA-G.9. A method of claim 1 , wherein the HLA-G expression in the HLA-G MSCs is assessed by detecting the corresponding mRNA or its transcript.10. A method of claim 1 , wherein the HLA-G expression in the HLA-G MSCs is assessed by detecting the cell surface expression of HLA-G.11. A method of ...

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16-03-2017 дата публикации

ACTIVATOR FOR MESENCHYMAL STEM CELLS, ACTIVATED MESENCHYMAL STEM CELLS, AND METHOD FOR PRODUCING SAME

Номер: US20170071984A1
Принадлежит: SAPPORO MEDICAL UNIVERSITY

[Problem] To activate an abnormal mesenchymal stem cell whose therapeutic effect is lost or reduced, or rather which has a disease-exacerbating effect so as to be in a state suitable for cell transplant therapy. 1. A method for producing an activated mesenchymal stem cell from an abnormal mesenchymal stem cell separated from a subject , comprisingtreating the abnormal mesenchymal stem cell with an extract from mammalian fetal appendage.2. The method according to claim 1 , wherein the fetal appendage is an umbilical cord tissue claim 1 , a placental tissue or a placental membrane.3. The method according to claim 1 , wherein the extract does not contain cells that are derived from the mammal and have proliferation potency.4. The method according to claim 1 , wherein the abnormal mesenchymal stem cell is a bone-marrow-derived mesenchymal stem cell.5. The method according to claim 1 , wherein the abnormal mesenchymal stem cell is separated from a subject with a disease.6. The method according to claim 5 , wherein the disease is diabetes claim 5 , an autoimmune disease claim 5 , a chronic inflammatory disease claim 5 , an allergic disease or osteoporosis.7. The method according to claim 5 , wherein the disease is diabetes or rheumatoid arthritis.812-. (canceled)13. A mesenchymal stem cell for the treatment and/or prevention of a disease claim 5 , wherein the cell is produced by the method comprisingtreating an abnormal mesenchymal stem cell separated from a subject with an extract from mammalian fetal appendage.14. The mesenchymal stem cell according to claim 13 , wherein the disease is diabetes or its complications claim 13 , an autoimmune disease claim 13 , a chronic inflammatory disease claim 13 , an allergic disease or osteoporosis.15. The mesenchymal stem cell according to claim 13 , wherein the disease is diabetic nephropathy claim 13 , diabetic retinopathy claim 13 , diabetic neuropathy or rheumatoid arthritis.16. A pharmaceutical composition comprising a ...

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16-03-2017 дата публикации

Bone grafts including osteogenic stem cells, and methods relating to the same

Номер: US20170072101A1
Принадлежит: Globus Medical Inc

Bone grafts and constructs including stem cells are provided. Example bone grafts include osteogenic stem cells seeded on a scaffold of osteoconductive cortico-cancellous chips and/or osteoinductive demineralized bone. Example constructs include extracellular matrix on a synthetic scaffold, in which the ECM is secreted from MSCs seeded onto the synthetic scaffold. Also provided are methods of making the present bone grafts and scaffolds. Further provided are methods of promoting bone healing and treating wound healing, by administering the present bone grafts and constructs to a mammal in need thereof. Also provided are kits that include the present bone grafts and/or constructs, or components thereof.

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07-03-2019 дата публикации

CULTURE MEDIA FOR MULTIPOTENT STEM CELLS

Номер: US20190071642A1
Автор: Park Hyeonggeun
Принадлежит:

A growth medium for culturing mesenchymal stem cells. The medium comprises a serum, a fibroblast growth factor, and either an L-cysteine, a glutathione, or an N-acetyl cysteine. Optionally, the medium can comprise various quantities of an epidermal growth factor, a hydrocortisone, a calcium chloride, an insulin, a pituitary extract, a selenium, a stromal-derived factor, a sodium pyruvate, a transferrin, and serum-free medium. 1. A growth medium for culturing mesenchymal stem cells comprising:a) a serum;b) a fibroblast growth factor; and i) an L-cysteine;', 'ii) a glutathione; or', 'iii) an N-acetyl cysteine., 'c) either2. The growth medium of claim 1 , further comprising at least one component comprising:a) an epidermal growth factor;b) a hydrocortisone;c) a calcium chloride;d) an insulin;e) a pituitary extract;f) a selenium;g) a stromal-derived factor;h) a sodium pyruvate;i) a transferrin; orj) a serum-free medium.3. The growth medium of claim 1 , wherein the growth medium comprises components in the following amounts:a) serum from about 0.1 percent to about 50 percent by volume;b) fibroblast growth factor from about 1 pg/mL to about 100 ng/mL; andc) L-cysteine, or glutathione, or N-acetyl cysteine from about 1 nM to about 100 mM.4. The growth medium of claim 2 , wherein the growth medium comprises the at least one component if present in the following amounts:a) epidermal growth factor from about 1 pg/mL to about 100 ng/mL;b) hydrocortisone from about 1 pg/mL about 100 μg/mL;c) calcium chloride from about 1 nM to about 100 mM;d) insulin from about 1 ng/mL to about 100 mg/mL;e) pituitary extract from about 1 pg/mL to about 100 mg/mL;f) selenium from about 1 pg/mL to about 100 mg/mL;g) stromal-derived factor from about 1 pg/mL to about 100 ng/mL;h) sodium pyruvate from about 1 ng/mL to about 100 mg/mL;i) transferrin from about from about 1 ng/mL to about 100 mg/mL; andj) serum free medium balanced to 100 percent volume.5. The growth medium of claim 1 , wherein the ...

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24-03-2022 дата публикации

STROMAL STEM CELLS

Номер: US20220090019A1
Принадлежит:

Stromal stem cells are prospectively isolated from human bone marrow then expanded into clonal populations and cultured and used, the isolation being on the basis of expression of a cell surface marker, wherein the cell surface marker binds an antibody and wherein said antibody cross reacts with a cell surface marker found on mouse stromal stem cells or rat stromal stem cells, and optionally also on a cell of at least one other mammalian species selected from mouse, rat, horse, rabbit and pig cells. Useful stromal stem cell populations are positive for SDC2. 1. A composition comprising: (i) a population of mammalian stromal stem cells , wherein 30% or more of the cells are positive for SDC2; and (ii) a cryopreservant , wherein the population of mammalian stromal stem cells exhibits 1000-fold or more colony forming units compared with native pre-sorted mononuclear cells.2. The composition of claim 1 , wherein the cryopreservant is dimethylsulfoxide.3. The composition of claim 1 , further comprising human serum albumin claim 1 , saline claim 1 , hyaluronic acid claim 1 , or collagen.4. The composition of claim 1 , wherein 50% or more of the cells are positive for SDC2.5. The composition of claim 1 , wherein 75% or more of the cells are positive for SDC2.6. The composition of claim 1 , wherein the cells are human cells.7. The composition of claim 1 , wherein the cells are negative for CD45.8. The composition of claim 1 , wherein the composition is suitable for injection.9. The composition of claim 1 , wherein the cells are derived from bone marrow.10. The composition of claim 1 , wherein the cells are derived from umbilical cord.11. The composition of claim 1 , wherein the cells are derived from adipose tissue claim 1 , skeletal muscle claim 1 , endometrium claim 1 , placenta claim 1 , umbilical cord blood claim 1 , or Wharton's jelly.12. The composition of claim 1 , wherein the population of mammalian stromal stem cells exhibits 1500-fold or more colony forming units ...

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18-03-2021 дата публикации

COMPOSITIONS AND METHODS FOR MODIFYING THE SURFACE OF CELLS AND METHODS OF USE

Номер: US20210077631A1
Принадлежит:

Described herein are compounds, compositions and methods for modification of the surface of a living cell with a therapeutically relevant targeting moiety. Also described herein are methods for treating disease states, such as acute myocardial ischemia or infarction, with said compositions, in a subject. 1. A composition comprising the compound of formula (I){'br': None, 'L-Y—X-T\u2003\u2003(I)'}whereinL is a phospholipid;Y is a poly(ethylene glycol);X is a linker derived from a reactive functional group; andT is a targeting moiety adapted to bind to a target ligand.2. The composition of claim 1 , wherein L is selected from the group consisting of 1 claim 1 ,2-dimyristoyl-sn-glycero-3-phosphoethanolamine claim 1 , 1 claim 1 ,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine and 1 claim 1 ,2-distearoyl-sn-glycero-3-phosphocholine.3. The composition of claim 1 , wherein L is 1 claim 1 ,2-dimyristoyl-sn-glycero-3-phosphoethanolamine.4. The composition of claim 1 , wherein the poly(ethylene glycol) has a molecular weight between about 2 kDa and about 10 kDa.5. The composition of claim 1 , wherein the poly(ethylene glycol) has a molecular weight of about 5 kDa.6. The composition of claim 1 , wherein the reactive functional group is selected from the group consisting of maleimide claim 1 , N-hydroxysuccinimide claim 1 , hydroxyl claim 1 , amino claim 1 , carboxyl claim 1 , thiol claim 1 , silane claim 1 , and azide.7. The composition of claim 1 , wherein the target ligand is SDF-1.8. The composition of claim 1 , wherein the target ligand is CRIP2.9. The composition of claim 1 , wherein T is selected from the group consisting of a protein claim 1 , a peptide claim 1 , a glycoprotein claim 1 , a glycopeptide claim 1 , a steroid claim 1 , a polysaccharide claim 1 , a hormone claim 1 , a cofactor claim 1 , a nucleic acid claim 1 , an antibody claim 1 , a chimeric antigen receptor claim 1 , and a drug.10. The composition of claim 1 , wherein T is a protein.11. The composition of ...

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18-03-2021 дата публикации

TISSUE-SPECIFIC DIFFERENTIATION MATRICES AND USES THEREOF

Номер: US20210079351A1
Автор: Chen Xiao-Dong
Принадлежит:

In some aspects, this invention provides a method of making a bone marrow-derived tissue-specific stem cell proliferation, expansion, isolation and rejuvenation extracellular matrix. In other aspects, this invention provides a method of making a tissue-specific fibroblast-derived stem cell differentiation extracellular matrix. Also provided are methods of using such a cell-derived preservation or differentiation matrices to induce tissue-specific differentiation of pluripotent cells, repair damaged tissue, and treat a subject having a physiologic deficiency using the same. 148.-. (canceled)49. A method of treating a subject having a physiologic deficiency comprising:a) contacting a sample containing MSCs with a rejuvenating matrix to produce rejuvenated MSCs; andb) introducing the rejuvenated MSCs into the subject,wherein the physiologic deficiency is treated.50. The method of claim 49 , wherein the sample is a human or murine sample.51. The method of claim 49 , wherein the rejuvenating matrix is a preservation matrix generated by bone marrow cells obtained from a subject that is younger than the subject having a physiologic deficiency.52. The method of claim 51 , wherein the subject is an elderly subject suffering from one or more of osteopenia claim 51 , osteoporosis claim 51 , sarcopenia and cachexia.53. The method of claim 49 , wherein the rejuvenating matrix is a 3D rejuvenating matrix.54106.-. (canceled) The present application is a continuation of U.S. patent application Ser. No. 15/463,003, filed Mar. 20, 2017, which is a divisional of U.S. patent application Ser. No. 13/821,288 (now U.S. Pat. No. 9,617,511), filed Apr. 9, 2013, which is a national phase under 35 U.S.C. § 371 of International Application No. PCT/US2011/050550, filed Sep. 6, 2011, which claims benefit of priority to U.S. Provisional Application Ser. No. 61/380,691 filed Sep. 7 2010 and U.S. Provisional Application No. 61/390,558 filed Oct. 6, 2010, the entire contents of each of which are ...

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18-03-2021 дата публикации

Systems and methods for collecting, processing, optimizing, and preparing stem cells for further use

Номер: US20210080358A1
Принадлежит: Elite Ip LLC

A system for collecting and processing a sample of an enriched population of mesenchymal stem cells in a matrix of body tissue in which the sample is separated into smaller segments to optimize the ability of the system to organize the stem cells into small working clusters with tissue. The tissue clusters are separated into optimized groupings for further processing and use in medical procedures.

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14-03-2019 дата публикации

MATERIALS AND METHODS FOR TREATMENT OF HEREDITARY HAEMOCHROMATOSIS

Номер: US20190076551A1
Принадлежит: CRISPR Therapeutics AG

Materials and methods for treating a patient with hereditary hemochromatosis (HHC), both ex vivo and in vivo, and materials and methods for modulating the expression, function, or activity of a haemochromatosis (HFE) gene in a cell by genome editing. 1. A method for editing a haemochromatosis (HFE) gene in a human cell by genome editing , the method comprising:introducing into the human cell one or more deoxyribonucleic acid (DNA) endonucleases to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near the HFE gene or other DNA sequences that encode regulatory elements of the HFE gene that results in a permanent deletion, insertion, correction, or modulation of expression or function of one or more mutations within or near or affecting the expression or function of the HFE gene and results in restoration of HFE protein activity.2. A method for inserting a haemochromatosis (HFE) gene in a human cell by genome editing , the method comprising:introducing into the human cell one or more deoxyribonucleic acid (DNA) endonucleases to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near a safe harbor locus that results in a permanent insertion of the HFE gene, and results in restoration of HFE protein activity.3. An ex vivo method for treating a patient with hereditary hemochromatosis (HHC) , the method comprising:creating a patient specific induced pluripotent stem cell (iPSC);editing within or near a haemochromatosis (HFE) gene or other DNA sequences that encode regulatory elements of the HFE gene of the iPSC, or editing within or near a safe harbor locus of the iPSC;differentiating the genome-edited iPSC into a hepatocyte; andimplanting the hepatocyte into the patient.4. The method of claim 3 , wherein the creating step comprises:isolating a somatic cell from the patient; andintroducing a set of pluripotency-associated genes into the somatic cell to induce the somatic cell to become a ...

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23-03-2017 дата публикации

READY-TO-PRINT CELLS AND INTEGRATED DEVICES

Номер: US20170079262A1
Принадлежит:

Disclosed herein are compositions, devices, and methods that provide cellular materials in ready to use formats for experimental, therapeutic, and tissue engineering protocols. For example, compositions containing frozen or non-frozen cell present as aggregates are disclosed. Also disclosed a compositions containing cellular materials that after storage are suitable for dispersion, e.g. by 3D printing. Also disclosed is a kit for producing bioink compositions. Also disclosed is a closed system device comprising a cell material composition described herein. 1. A composition comprising frozen cells in a cryopreservative agent , wherein the cells are formed into aggregates containing on average at least 1 ,000 cells per aggregate , and wherein the cell aggregates have a cell viability of at least 70% after being stored for at least 6 months at −60° C.2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. A composition comprising cells in a biopreservative agent , wherein the cells are formed into aggregates containing on average at least 1 ,000 cells per aggregate , and wherein the cell aggregates have a cell viability of at least 70% and retain the ability to fuse after being stored for at least 7 days at 4° C.7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. A composition comprising cells suspended in a viscous matrix , wherein the cells are at an average cell density of at least one million cells per milliliter , wherein the viscous matrix has a viscosity effective to maintain a cell density variance less than 10% for at least 48 hours , wherein the cells have a cell viability of at least 70% after being stored for at least 7 days at 4° C.12. The composition of claim 11 , wherein the cells are formed into aggregates containing on average at least 1 claim 11 ,000 cells per aggregate claim 11 , wherein the aggregates retain the ability to fuse after being stored for at least 7 days at 4° C.13. The composition of claim 12 , wherein the aggregates have a mean ...

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31-03-2022 дата публикации

METHODS AND COMPOSITIONS RELATING TO MESENCHYMAL STEM CELL EXOSOMES

Номер: US20220096560A1
Принадлежит: CHILDREN'S MEDICAL CENTER CORPORATION

The invention provides compositions comprising mesenchymal stem cell (MSC) derived exosomes, and methods of their use in subjects having certain lung diseases including inflammatory lung disease. 18-. (canceled)9. A method comprisingadministering to a subject having or at risk of developing a lung disease an effective amount of isolated mesenchymal stem cell (MSC) exosomes.1015-. (canceled)16. The method of claim 9 , wherein lung disease is inflammatory lung disease claim 9 , lung vascular disease claim 9 , or acute lung injury.17. The method of claim 16 , wherein the inflammatory lung disease is pulmonary hypertension claim 16 , asthma claim 16 , bronchopulmonary dysplasia (BPD) claim 16 , allergy claim 16 , or idiopathic pulmonary fibrosis.18. The method of claim 16 , wherein the acute lung injury is associated with sepsis or is ventilator-induced acute respiratory distress syndrome (ARDS).19. The method of claim 9 , wherein the subject has or is likely to develop schistosomiasis.20. The method of claim 9 , wherein the subject is an neonate.21. The method of claim 9 , wherein the subject is an infant.2223-. (canceled)24. The method of claim 9 , wherein the subject was born prematurely.2527-. (canceled)28. The method of claim 9 , wherein the isolated MSC exosomes are used together with a secondary agent.29. The method of claim 28 , wherein the secondary agent is a steroid claim 28 , an antioxidant claim 28 , or inhaled nitric oxide.3033-. (canceled)34. The method of claim 20 , wherein the isolated MSC exosomes are administered within 1 month of birth.35. The method of claim 9 , wherein the isolated MSC exosomes are administered intravenously.36. The method of claim 9 , wherein the isolated MSC exosomes are administered to lungs or trachea of the subject.37. The method claim 36 , composition claim 36 , use claim 36 , or isolated MSC exosomes of claim 36 , wherein the isolated MSC exosomes are administered by inhalation.3844-. (canceled)45. The method of claim 9 , ...

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26-03-2015 дата публикации

In vitro method for culturing stem cells

Номер: US20150087057A1

There is provided a method for culturing a stem cell in vitro. The method comprises providing a substrate surface coated with a coating comprising a molecule having a catechol moiety or a polymer thereof; and growing a stem cell on said coated substrate surface in a growth medium.

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23-03-2017 дата публикации

MATERIALS AND METHODS FOR EXPANSION OF STEM CELLS

Номер: US20170081638A1
Автор: MA TENG
Принадлежит:

The subject invention concerns novel and translatable materials and methods for expansion of stem cells, such as mesenchymal stem cells (MSC), that significantly improve translational success of the cells in the treatment of various conditions, such as stroke. The subject invention utilizes cell self-aggregation as a non-genetic means to enhance their therapeutic potency in a microcarrier bioreactor. The subject invention integrates a cell aggregation process in a scalable bioreactor system. In one embodiment of the method, thermally responsive microcarriers (TRMs) are utilized in conjunction with a bioreactor system. Cells are cultured in a container or vessel in the presence of the TRMs wherein cells adhere to the surface of the TRMs. Once cells are adhered to the TRMs they can be cultured at a suitable temperature for cell growth and expansion, e.g., at about 37° C. After a period of time sufficient for cell growth and expansion on the TRMs, the cell culture temperature is reduced so that the cells detach from the TRMs. The detached cells are allowed to form cell clusters that are then cultured under conditions such that the clusters aggregate to form 3D aggregates. The 3D aggregates can be collected and treated to dissociate the cells (e.g., using enzymatic treatment, such as trypsinization). Dissociated cells can then be used for transplantation in methods of treatment or for in vitro characterization and study. 1. A method for expanding a stem cell , wherein said method comprises culturing stem cells in a bioreactor system in the presence of a thermally responsive microcarrier (TRM) , wherein stem cells adhere to the surface of said TRM; growing the adhered stem cells for a sufficient period of time for the stem cells to increase in numbers; detaching the stem cells from the TRM by reducing the culture temperature to a critical solution temperature that results in said adhered cells detaching from the surface of said TRM; providing said detached cells ...

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31-03-2022 дата публикации

METHOD FOR MESENCHYMAL STEM CELL ISOLATION AND OSTEOBLAST DIFFERENTIATION

Номер: US20220098553A1
Принадлежит:

The present disclosure discloses a method for isolating osteoprogenitors like mesenchymal stem cells (MSCs) from clotted bone marrow and culturing with a platelet lysate obtained from a combination of discarded umbilical cord blood and maternal blood platelet-rich plasma (instead of non-human animal origin serum) and differentiating those MSCs into osteoblasts under sterile conditions for further therapeutic applications. Particularly, the present disclosure relates to a method for expansion of osteoblasts to make cell therapy products with a fixed cell dose, which are characterized and later cryopreserved for future use through its cell culture process. Further, the present disclosure relates to identifying specific gene expression from MSCs to osteoblast formation, an in-vitro differentiation process that replicates the in-vivo bone remodelling system. 1. A method for preparing mesenchymal stem cells suspension from a clotted bone marrow , said method comprising:a) obtaining a bone marrow sample, wherein the bone marrow sample comprises clotted bone marrow;{'sup': '3', 'b) chopping the clotted bone marrow into pieces of at least 2 mmto obtain chopped clotted bone marrow;'}c) contacting the chopped clotted bone marrow to at least one enzyme, or at least one protein, or combinations thereof in presence of a buffer to obtain a clotted bone marrow reaction solution;d) incubating the clotted bone marrow reaction solution at a temperature of at least 35° C. for a time of at least 20 minutes to obtain incubated clotted bone marrow reaction solution;e) contacting the incubated clotted bone marrow reaction solution of step (d) to a growth medium to obtain a suspension;f) mixing the suspension for a plurality of repeats;g) filtering the suspension of step (f) with a cell strainer to obtain a filtrate;h) centrifuging the filtrate to obtain a cell pellet; andi) dissolving the cell pellet with a nutrient medium to obtain a mesenchymal stem cell suspension, wherein the nutrient ...

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25-03-2021 дата публикации

FROZEN CELL CLUSTER AND METHOD FOR PRODUCING FROZEN CELL CLUSTER

Номер: US20210084893A1
Принадлежит:

A frozen cell cluster is a cell cluster in a frozen state in which mesenchymal stem cells are granularly formed. A method for producing the frozen cell cluster includes culturing a mesenchymal stem cell in a growth medium containing a factor that causes the mesenchymal stem cell to produce collagen, forming a granular cell cluster containing the collagen produced from the mesenchymal stem cell, and isolating the cell cluster from the growth medium and cryopreserving the cell cluster together with a cryopreservation agent. 1. A frozen cell cluster that is a cell cluster in a frozen state in which mesenchymal stem cells are granularly formed.2. The frozen cell cluster according to claim 1 , wherein the frozen cell cluster has a granular shape with a diameter of 0.5 mm to 1.5 mm.3. The frozen cell cluster according to claim 2 , wherein the frozen cell cluster has a granular shape with a diameter of 0.8 mm to 1.2 mm.4. A method for producing a frozen cell cluster claim 2 , comprising:culturing a mesenchymal stem cell in a growth medium containing a factor that causes the mesenchymal stem cell to produce collagen;forming a granular cell cluster containing the collagen produced from the mesenchymal stem cell; andisolating the cell cluster from the growth medium and cryopreserving the cell cluster together with a cryopreservation agent.5. The method for producing a frozen cell cluster according to claim 4 , wherein:a mesenchymal stem cell is cultured to form a cell sheet; anda periphery of the cell sheet is configured as a free edge to cause forming of a granular cell cluster by a self-aggregating effect.6. The method for producing a frozen cell cluster according to claim 5 , wherein the periphery of the cell sheet is made the free edge by culturing the mesenchymal stem cell in a culture vessel and allowing growth of the mesenchymal stem cell to reach confluence claim 5 , and separating an edge of the cell sheet adhering to a peripheral wall of the culture vessel from the ...

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25-03-2021 дата публикации

COMPOSITIONS AND METHODS FOR MODIFYING CELL SURFACE GLYCANS

Номер: US20210087541A1
Автор: Sackstein Robert
Принадлежит:

Methods and compositions for modifying glycans (e.g., glycans expressed on the surface of live cells or cell particles) are provided herein. 147.-. (canceled)48. A method of administering a population of modified cells to a subject comprising the steps of:(1) contacting a population of cells in vitro with a purified α-1,3-fucosyltransferase capable of transferring 1.0 μmole of fucose to an acceptor per minute at pH 6.5 at 37° C. in a physiologically acceptable solution comprising a fucose donor, without the input of divalent metal co-factors, thereby forming the population of modified cells comprising modified CD44 structures that bind E-selectin, and wherein the population of modified cells has a viability of at least 70% at 24 hours after the contacting with the α-1,3-fucosyltransferase; and(2) administering the population of modified cells to the subject.49. The method of claim 48 , wherein the population of modified cells is a population of stem cells or a population of differentiated cells.50. The method of claim 48 , wherein the population of modified cells is a population of hematopoietic stem cells claim 48 , a population of mesenchymal stem cells claim 48 , a population of tissue stem/progenitor cells claim 48 , a population of umbilical cord stem cells claim 48 , or a population of embryonic stem cells.51. The method of claim 48 , wherein the population of modified cells bind to one or more of E-selectin and L-selectin.52. The method of claim 48 , wherein the population of modified cells is a population of lymphocyte or leukocyte cells.53. The method of claim 48 , wherein the population of modified cells has a viability of at least 80% at 12 hours after the contacting with the α-1 claim 48 ,3-fucosyltransferase.54. The method of claim 48 , wherein the population of modified cells has a viability of at least 80% at 24 hours after the contacting with the α-1 claim 48 ,3-fucosyltransferase.55. The method of claim 48 , wherein the population of modified cells ...

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29-03-2018 дата публикации

MESENCHYMAL STEM CELLS EXPRESSING TNF-ALPHA RECEPTORS

Номер: US20180087032A1
Принадлежит: MESOBLAST INTERNATIONAL SARL

Mesenchymal stem cells which express TNF-α receptor Type I in an amount of at least 13 pg/10cells. Such mesenchymal stem cells inhibit the proliferation of lymphocytes and may be employed, in particular, in the treatment of graft-versus-host disease. 15-. (canceled)6. A method of treating a disease or disorder involving an immunological response in a subject comprising administering to the subject a population of mesenchymal stem cells that has been selected based on expression of TNF-α receptor Type I in an amount of at least 13 pg/10cells.7. The method of claim 6 , wherein the mesenchymal stem cells express TNF-α receptor Type I in an amount of at least 15 pg/10cells.8. The method of claim 6 , wherein the mesenchymal stem cells express TNF-α receptor Type I in an amount of at least 18 pg/10cells.9. The method of claim 6 , further comprising selecting the population of mesenchymal stem cells expressing TNF-α receptor Type I in an amount of at least 13 pg/10cells10. The method of claim 6 , wherein the immunological response is associated with an autoimmune disease.11. The method of claim 10 , where the autoimmune disease is selected from the group consisting of rheumatoid arthritis claim 10 , multiple sclerosis claim 10 , Type I diabetes claim 10 , Crohn's disease claim 10 , Guillain-Barré syndrome claim 10 , lupus erythematosus claim 10 , myasthenia gravis claim 10 , optic neuritis claim 10 , psoriasis claim 10 , Graves' disease claim 10 , Hashimoto's disease claim 10 , Ord's thyroiditis claim 10 , aplastic anemia claim 10 , Reiter's syndrome claim 10 , autoimmune hepatitis claim 10 , primary biliary cirrhosis claim 10 , antiphospholipid antibody syndrome claim 10 , opsoclonus myoclonus syndrome claim 10 , temporal arteritis claim 10 , acute disseminated encephalomyelitis claim 10 , Goodpasture's syndrome claim 10 , Wegener's granulomatosis claim 10 , coeliac disease claim 10 , pemphigus claim 10 , polyarthritis claim 10 , warm autoimmune hemolytic anemia claim 10 ...

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31-03-2016 дата публикации

Scheduled Feed

Номер: US20160090569A1
Автор: VANG Boah
Принадлежит: TERUMO BCT, INC.

Embodiments described herein generally provide for the scheduled feeding of cells in a cell expansion system. A schedule to proactively and automatically increase and/or maintain inlet rates of media to feed cells may be created, in which inlet rates to the intracapillary portion (or extracapillary portion) of a bioreactor may be increased or maintained according to the schedule. Such schedule may be conservative or aggressive or a combination thereof, for example. Multiple schedules may be used. Scheduled media exchanges may also be included. By following a feed schedule, the monitoring of metabolite levels may be optional. Inlet rates may be increased or maintained without manual manipulation. Media usage may also be more predictable. In an embodiment, a custom task(s) may be created to follow a desired feed schedule. In another embodiment, a pre-programmed task(s) may be used for the scheduled feeding of cells. 1. A method of feeding cells in a cell expansion system according to a schedule , the method comprising:coating a bioreactor;loading cells into the bioreactor; andfeeding the cells according to the schedule.2. The method of claim 1 , wherein the feeding the cells according to the schedule comprises increasing a first inlet rate into a portion of the cell expansion system according to the schedule.3. The method of claim 2 , wherein the portion of the cell expansion system comprises an intracapillary (IC) portion of the cell expansion system.4. The method of claim 2 , wherein the portion of the cell expansion system comprises an extracapillary (EC) portion of the cell expansion system.5. The method of claim 3 , wherein the intracapillary (IC) portion of the cell expansion system comprises an intracapillary (IC) circulation loop.6. The method of claim 4 , wherein the extracapillary (EC) portion of the cell expansion system comprises an extracapillary (EC) circulation loop.7. The method of claim 1 , wherein the cell expansion system comprises a closed system.8 ...

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19-03-2020 дата публикации

IMMUNOMODULATING CELL CIRCUITS

Номер: US20200085876A1
Принадлежит:

Provided herein are methods and compositions for dynamically controlling and targeting multiple arms of the immune system. Some aspects provide mesenchymal stem cells (MSCs) engineered to produce multiple effector molecules. In some instances, each effector molecule modulates a different cell type of the immune system or different functions of a cell. Also provided herein are methods of using the MSCs to treat or alleviate symptoms of inflammatory bowel disease (IBD), for example. 1. A mesenchymal stem cell engineered to produce two anti-inflammatory cytokines at levels sufficient to inhibit an inflammatory response.2. A mesenchymal stem cell of claim 1 , wherein the inflammatory response is inhibited by at least 20% relative to a control claim 1 , optionally wherein the control is an unmodified mesenchymal stem cell.3. The mesenchymal stem cell of or claim 1 , wherein the anti-inflammatory cytokines are selected from IL-4 claim 1 , IL-10 claim 1 , and IL-22.4. The mesenchymal stem cell of claim 3 , wherein the anti-inflammatory cytokines are IL-4 and IL-10.5. The mesenchymal stem cell of claim 3 , wherein the anti-inflammatory cytokines are IL-4 and IL-22.6. The mesenchymal stem cell of claim 3 , wherein the anti-inflammatory cytokines are IL-10 and IL-22.7. The mesenchymal stem cell of any one of - claim 3 , wherein the mesenchymal stem cell is derived from bone marrow claim 3 , adipose tissue claim 3 , or umbilical cord tissue.8. The mesenchymal stem cell of any one of - claim 3 , wherein the anti-inflammatory cytokine levels are sufficient to induce a regulatory T cell immunophenotype.9. The mesenchymal stem cell of any one of - claim 3 , wherein the anti-inflammatory cytokine levels are sufficient to inhibit production of inflammatory cytokine by stimulated T cells by at least 20% relative to a control claim 3 , optionally wherein the control is an unmodified mesenchymal stem cell.10. The mesenchymal stem cell of claim 9 , wherein the inflammatory cytokines are ...

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05-05-2022 дата публикации

METHODS FOR CULTURING MESENCHYMAL STEM CELLS, PRODUCTS THEREOF, AND APPLICATIONS THEREOF

Номер: US20220135947A1
Принадлежит:

The present disclosure provides a process for obtaining an expanded primed mesenchymal stem cell population. In the process, the MSCs are cultured in the culture medium comprising a corneal stromal stem cell derived-conditioned medium to obtain the expanded population of the primed mesenchymal stem cell population along with the mesenchymal stem cell derived-conditioned medium. Also, provided is a method of culturing the MSCs in 3D culture using a spheroid-based method or a microcarrier-based method, in order to obtain the expanded primed mesenchymal stem cell population. Further, an exosome preparation obtained from the expanded primed mesenchymal stem cell derived-conditioned medium is also disclosed herein. The present disclosure also discloses a composition comprising an expanded population of the primed mesenchymal stem cells, or a primed mesenchymal stem cell derived-conditioned medium, or an exosome preparation, or combinations thereof.

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07-04-2016 дата публикации

Induction Medium & Methods for Stem Cell Culture & Therapy

Номер: US20160095885A1
Автор: BETANCOURT Aline
Принадлежит:

Novel MSC stem-cell culture and therapy methods and culture medium compositions for the purpose of inducing, activating, or priming discrete uniform cell phenotypes to selectively promote or suppress inflammation and immunity, yielding primed, activated, or induced cells used in cell-based therapy. 1. An induction medium for inducing a cultured population of MSC stem cells , comprising:a Toll-like receptor (TLR) ligand or TLR-ligand inducer;erythropoietin (EPO);exposure to hypoxia or hypoxia mimetic; andother known, standard culture-medium components;where said TLR ligand induces said MSC stem cells in a predicable manner, yielding expanded and induced, primed, or activated populations of MSC stem cells.2. The induction medium of claim 1 , where said TLR ligand amount is between about 0.10 picomolar (pM) and about 100 millimolar (mM) claim 1 , or equivalent TLR-ligand inducer amount; said erythropoietin (EPO) amount is between about 0.5 mU/mL and about 50 mU/mL; said exposure to hypoxia is about 0.5% to about 2% oxygen conditions; and said hypoxia mimetic further comprises cobalt chloride or desferrioxamine claim 1 , at a concentration of about 10 uM to about 1 mM.3. The induction medium of claim 1 , where said TLR ligand further comprises claim 1 , exclusively or in various combinations claim 1 , 1L4 claim 1 , IL13 claim 1 , poly(A:U) claim 1 , poly(I:C) claim 1 , aminoalkyl glucosaminide 4-phosphates claim 1 , interferons claim 1 , TNF-alpha claim 1 , GM-CSF claim 1 , and lipopolysaccharide (IPS).4. The induction medium of claim 1 , where said TLR ligand further comprises claim 1 , exclusively or in various combinations claim 1 , 1L4 claim 1 , IL13 claim 1 , poly(A:U) claim 1 , poly(I:C) claim 1 , or substitutes thereof.5. The induction medium of claim 1 , where said TLR ligand further comprises claim 1 , exclusively or in various combinations claim 1 , aminoalkyl glucosaminide 4-phosphates claim 1 , interferons claim 1 , TNF-alpha claim 1 , GM-CSF claim 1 , ...

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06-04-2017 дата публикации

IN VITRO PRE-CONDITIONED BONE MARROW-DERIVED MESENCHYMAL STEM CELLS AND USES THEREOF

Номер: US20170095511A1
Принадлежит:

Disclosed is a composition including: an isolated in vitro pre-conditioned population of adult bone marrow derived mesenchymal stem cells (BMSCs), wherein the BMSCs express neuronal markers, and wherein the neuronal markers are PGP9.5, NSE, Tuj1, HuC/D and neuronal nitric oxide synthase (nNOS). Methods of preparing the BMSCs are also provided. In addition, the present disclosure is directed to a method of treating an enteric nervous system-related disorder including: administering to a subject in need thereof a pharmaceutical composition including the in vitro pre-conditioned BMSC population and a pharmaceutically acceptable carrier. 2. The composition of claim 1 , wherein the in vitro pre-conditioning comprises:providing a population of mesenchymal stem cells from a bone marrow;culturing the population of mesenchymal stem cells in a medium comprising a glial cell derived neurotrophic factor and a fetal gut culture medium.3. The composition of claim 1 , wherein about 80% of the cells in the in vitro pre-conditioned BMSC population express PGP9.5 claim 1 , about 80% of the cells in the in vitro pre-conditioned BMSC population express NSE claim 1 , about 75% of the cells in the in vitro pre-conditioned BMSC population express Tuj1 claim 1 , about 73% of the cells in the in vitro pre-conditioned BMSC population express HuC/D and about 75% of the in vitro pre-conditioned BMSC population express nNOS.4. The composition of claim 1 , wherein the in vitro pre-conditioned BMSCs are capable of maintaining a neuronal-like phenotype in vivo for at least 28 days.5. The composition of claim 1 , wherein the in vitro pre-conditioned BMSCs are human cells.6. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.7. The composition of claim 1 , wherein the in vitro pre-conditioned BMSC population are labeled with a bio-imaging agent.8. A method of treating an enteric nervous system-related disorder comprising:administering to a subject in need thereof a ...

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28-03-2019 дата публикации

CELL CULTURE BASE MATERIAL FOR TRAIT INDUCTION CONTROL OF MESENCHYMAL STEM CELLS AND TRAIT CONTROL METHOD THEREOF

Номер: US20190093060A1
Автор: MAENO Emi, Tabata Yasuhiko
Принадлежит:

A cell culture base material for trait induction control of mesenchymal stem cells including an uneven pattern on a surface to which cells adhere and of which the width of the unevenness is greater than or equal to 50 nm and less than 1,000 nm. A trait control method of mesenchymal stem cells includes culturing mesenchymal stem cells on the cell culture base material for trait induction control of mesenchymal stem cells. 1. A cell culture base material for trait induction control of mesenchymal stem cells , comprising an uneven pattern on a surface to which cells adhere , and of which the width of the unevenness is greater than or equal to 50 nm and less than 1 ,000 nm.2. The cell culture base material for trait induction control of mesenchymal stem cells according to claim 1 , wherein the uneven pattern has a lattice shape claim 1 , a radial shape claim 1 , a shape in which polygons are continuously formed on a plane claim 1 , a labyrinth shape claim 1 , a linear shape claim 1 , or a dot shape.3. A trait control method of mesenchymal stem cells claim 1 , comprising culturing mesenchymal stem cells on the cell culture base material for trait induction control of mesenchymal stem cells according to .4. A trait control method of mesenchymal stem cells claim 2 , comprising culturing mesenchymal stem cells on the cell culture base material for trait induction control of mesenchymal stem cells according to .5. The trait control method of mesenchymal stem cells according to claim 3 , wherein the mesenchymal stem cells secrete one or more anti-inflammatory factors.6. The trait control method of mesenchymal stem cells according to claim 4 , wherein the mesenchymal stem cells secrete one or more anti-inflammatory factors. The present invention relates to a cell culture base material for trait induction control of mesenchymal stem cells and a trait control method thereof. Priority is claimed on Japanese Patent Application No. 2017-187523, filed in Japan on Sep. 28, 2017, the ...

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26-06-2014 дата публикации

Stem cell culture medium and its applications as well as a stem cell culture method

Номер: US20140178987A1
Принадлежит:

The present invention discloses a stem cell culture medium and its applications as well as a stem cell culture method. The said stem cell culture medium contains no serum. The said stem cell culture medium contains amino acids, vitamins, salts, lipids, cytokines and protein polypeptides. The said stem cell culture medium is suitable for rapid culture of stem cells derived from human and mammalian tissues, including but not limited to, adipose mesenchymal stem cells, bone marrow mesenchymal stem cells and umbilical cord blood stem cells. The said culture medium can increase the proliferation speed of the stem cells 3-5 times, without any affects on their differentiation potentials. Comparing the said stem cell culture medium to a routine culture medium, the said culture medium is not only able to proliferate stem cells derived from different sources more rapidly and achieve more proliferation generations, but also keep their differentiation potentials well. 4. An application of the stem cell culture medium of claim 1 , wherein claim 1 , the said stem cell culture medium is used for culturing stem cells.5. The application of the said stem cell culture medium of claim 4 , wherein claim 4 , the stem cells include but not limited to stem cells derived from human and mammal.6. The application of the said stem cell culture medium of claim 4 , wherein claim 4 , the stem cells are isolated from various tissues or organs;the said tissues and organs include but not limited to, bone marrow, umbilical cord, adipose tissue, brain tissue, retina, heart, liver, lung and skin.7. A stem cell culture method claim 1 , using the stem cell culture medium as described in claim 1 , wherein claim 1 , coat the culture dish with materials promoting stem cell adhesion before culturing stem cells claim 1 , then add in the said stem cell culture medium and stem cells in sequence.8. A stem cell culture method of claim 7 , wherein claim 7 , the said materials applied to promote stem cell adhesion ...

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26-06-2014 дата публикации

MEMBRANE-SEPARATION-TYPE CULTURE DEVICE, MEMBRANE-SEPARATION-TYPE CULTURE KIT, STEM CELL SEPARATION METHOD USING SAME, AND SEPARATION MEMBRANE

Номер: US20140178992A1

A membrane separation culture device includes an upper structure including a vessel in which at least a portion of the bottom thereof is formed with a separation membrane having pores that allow stem cells to permeate therethrough, and a lower structure including a vessel that retains a fluid in which the membrane of the upper structure is immersed. 1. A membrane separation culture device comprising:an upper structure comprising a vessel in which at least a portion of the bottom thereof is formed with a separation membrane having pores that allow stem cells to permeate therethrough; anda lower structure comprising a vessel that retains a fluid in which the membrane of the upper structure is immersed.2. The membrane separation culture device according to claim 1 , wherein the separation membrane comprises:a base material membrane consisting of a hydrophobic polymer; anda functional layer formed by allowing one or more hydrophilic polymers selected from a vinyl pyrrolidone polymer, a polyethylene glycol polymer and a vinyl alcohol polymer to bind to the surface of the base material membrane via a covalent bond; whereinweight percentage of the hydrophilic polymer(s) constituting the functional layer is 1.5% to 35% based on the total weight of the separation membrane.3. The membrane separation culture device according to claim 1 , wherein the size of the pore is 3 μm to 10 μm and the density of the pore is 1×10to 4×10pores/cm.4. The membrane separation culture device according to claim 1 , comprising a plurality of the upper structures claim 1 , andfurther comprising a frame body accommodated in the lower structure and comprises a plate-like member having a plurality of holes each established to lock the plurality of the upper structures.5. The membrane separation culture device according to claim 1 ,comprising a plurality of the upper structures, and further comprising a frame body accommodated in the lower structure and comprises a plate-like member having a plurality ...

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16-04-2015 дата публикации

CARDIAC MUSCLE REPAIR OR REGENERATION USING BONE MARROW-DERIVED STEM CELLS

Номер: US20150104431A1
Принадлежит:

Disclosed are compositions and methods for repairing and/or regenerating cardiac tissue by administering adult bone marrow-derived stem cells to an individual. These cells can be administered as a liquid injectible or as a preparation of cells in a matrix which is or becomes solid or semi-solid. The cells can be genetically modified to enhance myocardial differentiation and integration. Also disclosed is a method for replacing cells ex vivo in a heart valve for implantation. 1. A cell preparation comprising adult bone marrow-derived stem cells in a dose effective to augment ventricular function in the heart of a subject in need thereof.2. The cell preparation of claim 1 , wherein the stem cells are capable of differentiating into at least one cell type of each of the endodermal claim 1 , ectodermal claim 1 , and mesodermal embryonic lineages.3. The cell preparation of claim 1 , wherein the dose comprises about 0.02 to about 150 milliliters of a pharmaceutically acceptable liquid medium and wherein the stem cells are at a concentration of about 10 to about 40 million cells per milliliter.4. The cell preparation of claim 1 , wherein the stem cells have an induced expression of at least one cardiac specific marker.5. The cell preparation of claim 4 , wherein the at least one cardiac specific marker is myosin heavy chain claim 4 , sarcoplasmic reticulum calcium ATPase claim 4 , or connexin 43.6. The cell preparation of claim 4 , wherein the induced expression of at least one cardiac specific marker results from (i) co-culturing the stem cells with cardiac cells claim 4 , (ii) use of chemical fusigens to create heterokaryons of the stem cells with cardiomyocytes claim 4 , (iii) incubating the stem cells with extracts of mammalian hearts claim 4 , (iv) treatment of the stem cells with growth factors claim 4 , differentiating agents claim 4 , or both claim 4 , (v) mechanical or electrical stimulation of the stem cells claim 4 , or (vi) mechanical or electrical coupling of ...

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16-04-2015 дата публикации

IMPLANTABLE SILK-BASED TISSUE PROSTHESES

Номер: US20150104514A1
Принадлежит:

A silk fiber based matrix composition comprising spider silk that can be biodegradable, from the spider species (or from genetically engineered bacteria making silk), and in the form of a mesh or film. 1. A tissue prosthesis comprising a matrix of sericin-extracted silkworm fibroin fibers , said fibers being biocompatible and helically organized into fiber bundles , wherein said matrix supports ingrowth of cells around said fibroin fibers and is biodegradable.2Bombyx mori. The prosthesis as recited in claim 1 , wherein the silk-fiber based matrix comprises fibroin fibers obtained from silkworm.3. The prosthesis as recited in claim 1 , wherein the matrix comprises a composite of the sericin-extracted fibroin fibers and collagen fibers.4. The prosthesis as recited in claim 1 , wherein the matrix comprises a composite of the sericin-extracted fibroin fibers and one or more silk foams claim 1 , films claim 1 , meshes or sponges.5. The prosthesis as recited in claim 1 , wherein the matrix comprises a composite of the sericin-extracted fibroin fibers and one or more degradable polymers selected from group consisting of Collagens claim 1 , Polylactic acid or its copolymers claim 1 , Polyglycolic acid or its copolymers claim 1 , Polyanhydrides claim 1 , Elastin claim 1 , Glycosamino glycans claim 1 , and Polysaccharides.6. The prosthesis as recited in claim 1 , further comprising pluripotent or fibroblast cells seeded on said matrix.7. The prosthesis as recited in claim 6 , wherein said pluripotent or fibroblast cells are autologous.8. The prosthesis as recited in claim 7 , wherein said pluripotent or fibroblast cells are allogeneic.9. The prosthesis as recited in claim 7 , wherein said pluripotent cells are selected from the group consisting of bone marrow stromal cells and adult or embryonic stem cells.10. The prosthesis as recited in claim 7 , wherein said fibroblast cells are mature human ACL fibroblast cells.11. The prosthesis as recited in in the shape of a smooth ...

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13-04-2017 дата публикации

MANAGEMENT OF ISCHEMIA USING POOLED MESENCHYMAL STROMAL CELL COMPOSITION

Номер: US20170100434A1
Принадлежит:

The present disclosure relates to composition comprising pooled and expanded allogeneic mesenchymal Stromal cells (MSCs) and a method for management of Ischemia using the composition thereof. In particular, the disclosure relates to bone marrow derived pooled and expanded allogeneic MSC compositions with effective dosage ranges and modes/route of administration for effective management of Ischemia. The disclosure also relates to the use of conditioned medium rich in bioactive factors in combination with the cell composition for managing ischemic conditions. 1. A composition comprising pooled and expanded allogeneic mesenchymal stromal cells in an amount ranging from about 1 million cells to 1000 million cells , optionally along with pharmaceutically acceptable excipient , for use in treating ischemia in a subject , wherein said composition is administered intramuscularly through a combination of at least two sites selected from group comprising calf muscle region , thigh region , at or along or in the course of constricted vessel and locally at or near the site affected by the ischemia.2. A method of treating ischemia in a subject having or suspected of having the ischemia , said method comprising acts of administering a composition comprising pooled and expanded allogeneic mesenchymal stromal cells at a dose ranging from about 0.5 million cells per kg of body weight of the subject to 5 million cells per kg of body weight of the subject , optionally along with pharmaceutically acceptable excipient to the subject , wherein said composition is administered intramuscularly through a combination of at least two sites selected from group comprising calf muscle region , thigh region , at or along or in the course of constricted vessel and locally at or near the site affected by the ischemia.3. The composition for use as claimed in claim 1 , wherein the mesenchymal stromal cells are derived from a source selected from a group comprising bone marrow claim 1 , adipose tissue ...

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26-03-2020 дата публикации

METHOD AND COMPOSITION FOR INDUCING CHONDROGENESIS OR TENOGENESIS IN MESENCHYMAL STEM CELLS

Номер: US20200095552A1
Принадлежит:

A cell medium for in vitro inducing chondrogenesis or tenogenesis in mesenchymal stem cells (MSCs). The medium is a glucose medium supplemented with at least one growth factor is chosen from the group of fibroblast growth factors (FGF) or the group of transforming growth factors (TGF), and the FGF or TGF is present in a total concentration of between 1 and 15 ng/ml. In both cases, IGF can be added to enhance the induction process. The use of the cell medium, a method for inducing isolated mesenchymal stem cells (MSCs) and a cell composition obtained by the method are also provided. 1. A method for inducing chondrogenesis in MSCs , comprising culturing said MSCs in an inducing cell medium , wherein said medium comprises a glucose medium supplemented with at least one growth factor selected from the group consisting of TGFα , TGFβ1 , TGFβ2 , TGFβ3 , and any combination thereof , wherein the growth factor is present at a total concentration of between 1 and 15 ng/ml in said medium.2. The method according to claim 1 , wherein said growth factor is present in a total concentration of between 2 and 10 ng/ml.3. The method according to claim 2 , wherein said growth factor is present in a total concentration of between 3.5 and 5.5 ng/ml.4. The method according to claim 1 , wherein said inducing cell medium further comprises a growth factor selected from the group consisting of IGF-1 claim 1 , IGF-2 claim 1 , IGF-I and any combination thereof in a concentration of between 10 and 225 ng/ml.5. The method according to claim 1 , wherein said MSCs are seeded at a density of 2 to 30×10MSCs/cm.6. The method according to claim 1 , wherein said MSCs are cultured for a period of 1-7 days in inducing medium.7. The method according to claim 1 , wherein said MSCs are isolated from mammalian blood.8. A composition comprising MSCs induced towards chondrocytes claim 1 , wherein said chondrocytes are obtained by culturing said MSCs in an inducing cell medium claim 1 , wherein said medium ...

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08-04-2021 дата публикации

Tissue-engineered three-dimensional model for tumor analysis

Номер: US20210102170A1
Принадлежит: Columbia University of New York

A 3D decellularized bone scaffold seeded with cancer cells, such as prostate cancer cells or Ewing's sarcoma is provided. The three-dimensional includes Ewing's sarcoma (ES) tumor cells; and an engineered human bone scaffold. The engineered human bone scaffold further includes osteoblasts that secrete substance of the human bone, and osteoclasts that absorb bone tissue during growth and healing. The engineered human bone scaffold includes the tissue engineered three-dimensional model which recapitulates the osteolytic process. The engineered human bone scaffold is engineered by co-culturing of osteoblasts and osteoclasts. The osteoblast is produced by cell differentiation process from mesenchymal stem cells. The osteoclast is produced by cell differentiation from human monocytes, wherein the human monocytes are isolated from buffy coats. The scaffold can be used with cancer cell lines to identify therapeutic targets to slow, stop, and reverse tumor growth and progression as well as to predict the efficacy of potential therapeutics.

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21-04-2016 дата публикации

Methods and Compositions for Optimized Expansion and Implantation of Mesenchymal Stem Cells

Номер: US20160106780A1
Принадлежит:

Compositions and methods are provided for the optimized expansion and implantation of mesenchymal stem cells into a patient in need thereof. Autologous mesenchymal stem cells (MSCs) to a patient in need of MSCs are harvested, expanded within novel growth parameters under the influence of autologous growth factors located on the patient's platelets. 132-. (canceled)33. A method of expanding mesenchymal stem cells (MSC) in vitro for use in an implant to regenerate cartilage , the method comprising:{'sup': th', 'th, '(a) obtaining mesenchymal stem cells (MSCs) from an older patient in the 5to 7decade of life who is diagnosed with osteoarthritis, avascular necrosis, or severe degenerative joint disease;'}(b) expanding the MSCs with a growth medium comprising the patient's platelet lysate in an initial amount of between 5% and 20% of the growth medium for at least one passage to obtain at least 10 million to 100 million cells; (i) a doubling time of about 1 to about 3 days;', {'br': None, 'Surface area x(%Confluence)/Cell Number;'}, '(ii) cellular confluence greater than about 27 calculated according to the equation'}], '(c) determining whether the MSCs of step (b) are outside the scope of one or more of the following parameters '(iv) greater than 30% of MSCs without a spindle shape; and', '(iii) random distribution of MSCs as a monolayer culture; or'}(d) adjusting the culture conditions in at least one following passage wherein the MSC are outside of the scope of at least one parameter in step (c) by at least one of: adjusting the amount of platelet lysate in the growth medium to between 15-20% platelet lysate, or by reseeding the MSC at a higher density than used in the original seeding;wherein the expanded MSCs are capable of regenerating new cartilage when implanted into the patient at a site in need thereof no later than the tenth ex-vivo passage.34. The method of further comprising implanting the expanded MSC into a site in need thereof and in-vivo monitoring of ...

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19-04-2018 дата публикации

CULTURE MEDIUM FOR PROLIFERATING STEM CELL, WHICH CONTAINS SULFATED COMPOUND

Номер: US20180105798A1
Принадлежит: AJINOMOTO CO., INC.

A medium which comprises a fibroblast growth factor (FGF), and a sulfated compound or a pharmaceutically acceptable salt thereof at a concentration which promotes the growth of a stem cell in the presence of FGF, is useful for culturing stem cells. 122-. (canceled)23: A method for culturing a stem cell , comprising culturing the stem cell in a medium comprising:a fibroblast growth factor (FGF), anda sulfated compound or a pharmaceutically acceptable salt thereof,wherein said sulfated compound or a pharmaceutically acceptable salt thereof is present in said medium at a concentration that promotes the growth of said stem cell in the presence of FGF, andwherein the sulfated compound content is not more than 250 ng/ml when the sulfated compound is a sulfated polysaccharide.24: The method according to claim 23 , wherein said sulfated compound or pharmaceutically acceptable salt thereof is a sulfated saccharide or a pharmaceutically acceptable salt thereof claim 23 , wherein the sulfated saccharide content is not more than 250 ng/ml when the sulfated saccharide is a sulfated polysaccharide.26: The method according to claim 24 , wherein said sulfated saccharide or pharmaceutically acceptable salt thereof is at least one compound selected from the group consisting of a sulfated monosaccharide claim 24 , a sulfated disaccharide claim 24 , a sulfated polysaccharide claim 24 , a sulfated sugar alcohol claim 24 , and a sulfated cyclitol claim 24 ,or a pharmaceutically acceptable salt of said at least one compound.27: The method according to claim 24 , wherein the content level of sulfur in the sulfated saccharide or pharmaceutically acceptable salt thereof is not less than 5 wt %.28: The method according to claim 24 , wherein said sulfated saccharide or pharmaceutically acceptable salt thereof is at least one compound selected from the group consisting of dextran sulfate Na claim 24 , cellulose SONa claim 24 , xanthan gum SONa claim 24 , pectin SONa claim 24 , fucoidan claim 24 ...

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20-04-2017 дата публикации

IMPROVED STEM CELL COMPOSITION

Номер: US20170107495A1
Принадлежит: MESOBLAST INTERNATIONAL SARL

The disclosure provides stem cells which express high levels of Angeopoetin-1 (Ang1) and methods for their production. Such stem cells may be used in a range of therapeutic application. 1. A composition comprising genetically unmodified stem cells wherein said genetically unmodified stem cells express angiopoietin-1 (Ang1) in an amount of at least 0.1 μg/10cells.2. The composition of wherein said stem cells express Ang1 in an amount of at least 0.5 μg/10cells.3. The composition of wherein said stem cells express Ang1 in an amount of at least 0.7 μg/10cells.4. The composition of wherein said stem cells express Ang1 in an amount of at least 1 μg/10cells.5. The composition of any one of to claim 1 , wherein said stem cells express Vascular Endothelial Growth Factor (VEGF) in an amount less than about 0.05 μg/10cells.6. The composition of any one of to claim 1 , wherein said stem cells express VEGF in an amount less than about 0.05 μg/10cells.7. The composition of any one of to claim 1 , wherein said stem cells express VEGF in an amount less than about 0.03 μg/10cells.8. The composition of any one of to claim 1 , wherein said stem cells express Ang1:VEGF at a ratio of at least about 2:1.9. The composition of any one of to claim 1 , wherein said stem cells express Ang1:VEGF at a ratio of at least about 10:1.10. The composition of any one of to claim 1 , wherein said stem cells express Ang1:VEGF at a ratio of at least about 20:1.11. The composition of any one of to claim 1 , wherein said stem cells express Ang1:VEGF at a ratio of at least about 30:1.12. The composition of any one of to claim 1 , wherein said stem cells express Ang1:VEGF at a ratio of at least about 50:1.13. The composition of any one of to claim 1 , wherein said stem cells are mesenchymal stem cells.14. The composition of wherein said stem cells are mesenchymal precursor cells.15. The composition of any one of to claim 13 , further comprising an acceptable pharmaceutical carrier.16. An in vitro method for ...

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29-04-2021 дата публикации

Compositions and methods for production of exofucosylated cells for clinical applications

Номер: US20210123024A1
Автор: Robert Sackstein
Принадлежит: Brigham and Womens Hospital Inc

The present disclosure provides, inter alia, compositions and methods for detecting changes in level of expression of cell-surface Type 2 terminal lactosamines on a population of cultured cells propagated under different conditions. The disclosure also provides compositions and methods for enforcing stably expressed glycans on human cells. In certain embodiments, the compositions and/or methods utilize one or more members of the α(1,3)-fucosyltransferase family. In certain embodiments, glycoengineered CD44 glycosylated product (e.g. HCELL) is stable for at least 48 hours at 4° C., with retained expression after cell cryopreservation.

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28-04-2016 дата публикации

HYPOXIA-CULTURED MESENCHYMAL STEM CELLS FOR TREATING ATHEROSCLEROTIC LESIONS

Номер: US20160113968A1
Автор: Hung Shih-Chieh
Принадлежит:

A method and a pharmaceutical composition for treating an atherosclerotic lesion are provided, including administering a subject in need thereof a therapeutically effective amount of a composition comprising hypoxia-cultured MSCs obtained by culturing auto- or allo-MSCs under low oxygen conditions. 1. A method for treating an atherosclerotic lesion , comprising administering a subject in need thereof a therapeutically effective amount of a composition comprising hypoxia-cultured mesenchymal stem cells (MSCs).2. The method of claim 1 , which comprises administering a subject in need thereof a therapeutically effective amount of a composition comprising hypoxia-cultured MSCs obtained by culturing auto- or allo-MSCs under low oxygen conditions less than 10% oxygen.3. The method of claim 1 , wherein the atherosclerotic lesion is associated with coronary artery disease claim 1 , stroke claim 1 , aortic aneurysm claim 1 , or peripheral arterial disease.4. The method of claim 1 , wherein the atherosclerotic lesion is selected from a group consisted of coronary atherosclerosis claim 1 , cerebral atherosclerosis claim 1 , aortic atherosclerosis claim 1 , and renal artery atherosclerosis.5. The method of claim 1 , wherein the composition comprising hypoxia-cultured MSCs is administering through intravenous injection claim 1 , intracoronary injection claim 1 , intracardiac injection claim 1 , intraperitoneal injection claim 1 , or local application.6. The method of claim 5 , wherein the composition comprising hypoxia-cultured MSCs is administering once or more in a therapeutic regimen.7. The method of claim 1 , wherein the hypoxia-cultured MSCs secrete cytokine IL8 to restore the endothelial function.8. The method of claim 1 , wherein levels of phospho-Akt claim 1 , phospho-endothelial nitric oxide synthase (eNOS) and total eNOS claim 1 , and nitrogen oxide (NO) production in the subject are increased through the administration of the composition comprising hypoxia-cultured ...

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