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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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Применить Всего найдено 8714. Отображено 100.
01-03-2012 дата публикации

Differentiation of Pluripotent Stem Cells

Номер: US20120052576A1
Автор: Alireza Rezania
Принадлежит: Janssen Biotech Inc

The present invention provides methods to promote the differentiation of pluripotent stem cells into insulin producing cells. In particular, the present invention provides a method utilizing an agent that degrades retinoic acid to produce a population of pancreatic endocrine precursor cells.

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Номер записи: 1
22-03-2012 дата публикации

Method For Enucleating Nucleated Erythrocyte, And Enucleation Inducer

Номер: US20120070897A1
Автор: Eriko Shimamura, Hiroki Shimada, Toshihisa Hatta
Принадлежит: KANAZAWA MEDICAL UNIVERSITY

Provided is a factor capable of inducing enucleation, which is a final stage of erythrocyte differentiation, within a short time. More particularly, provided are a method of inducing enucleation, which is a final stage of erythrocyte differentiation, within a short time by adding a compound derived from proopiomelanocortin (POMC) to an undifferentiated (nucleated) erythrocyte, and an enucleation inducer including the compound.

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Номер записи: 2
29-03-2012 дата публикации

Animal-free cell culture method

Номер: US20120077268A1
Автор: Brigitte Ghislaine Louise Aerts, Carine Maggetto, Isabelle Solange Lucie Knott, Marie-Monique Jane Gonze, Yves Jules Maurice Ghislain
Принадлежит: GLAXOSMITHKLINE BIOLOGICALS SA

The present invention relates to a process for culturing animal cells, e.g., human, diploid anchorage-dependent cells, in the absence of exogenous components of primary animal origin. In particular, the invention provides cell culture media substantially free of exogenous components of primary and secondary animal origin which comprises at least one, more preferably several, exogenous animal-free growth factors. The present invention also relates to a process for cultivating animal cells using a protease of non-animal origin for passaging cells.

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Номер записи: 3
26-04-2012 дата публикации

Regionalised endoderm cells and uses thereof

Номер: US20120100115A1
Автор: Gillian Mary Morrison, Ifigenia Oikonomopoulou, Joshua Mark Brickman
Принадлежит: University of Edinburgh

The present invention relates to the generation of anterior definitive endoderm (ADE) cells from embryonic stem cells and the differentiation of such cells to, for example, pancreatic or liver cells. The invention also relates to cell lines, cell culture methods, cells markers and the like and their potential uses in a variety of applications.

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Номер записи: 4
03-05-2012 дата публикации

Human Late Stage Motor Neuron Progenitor Cells and Methods of Making and Using Same

Номер: US20120107934A1
Автор: Aleksandra Poole
Принадлежит: California Stem Cells Inc

Motor neuron progenitor (MNP) cells and populations of MNP cells, are provided, in particular, populations of human late stage MNP cells having a purity of greater than about 65% late stage MNP cells and high-purity populations of MNP cells having greater than 95% viable cells, as well as method of making and using the same, including deriving late stage MNP cells from pluripotent embryonic stem cells, producing high-purity populations of late stage MNP cells, producing populations of viable MNP cells, transporting viable MNP cells, and transplanting MNP cells.

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Номер записи: 5
17-05-2012 дата публикации

Anti-estrogen and immune modulator combinations for treating breast cancer

Номер: US20120121620A1
Автор: David A. Sirbasku
Принадлежит: Individual

Compositions for treating cancers of mucosal tissues including breast, prostate, ovary, colon are disclosed which include various combinations of new or conventional anti-estrogen compounds, aromatase inhibitors, immune modulators, immune inhibitors, immune inhibitor mimicking compounds and steroid or thyroid hormones. Methods of predicting susceptibility of a cancer of mucosal origin to treatment with a composition containing an immune inhibitor or an immune inhibitor mimicking compound are also disclosed. Preferred methods include identifying in a specimen of cancer cells the presence of a Poly-Ig (Fe) receptor or Poly-Ig-like (Fc) receptor capable of binding to an immune inhibitor or an immune inhibitor mimicking compound and of mediating immune inhibition of cancer cell growth.

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Номер записи: 6
24-05-2012 дата публикации

Method of preparing pluripotent stem cells

Номер: US20120129256A1
Автор: Mariya A. Lagar'kova, Mariya V. Shutova, Sergey L. Kiselev
Принадлежит: OBSCHESTVO S OGRANICHENNOI OTVETSTVENNOSTYU "LABORATORIA KLETOCHNYKH TEKHNOLOGIY\

The invention relates to biotechnology, and particularly to the preparation of pluripotent stem cells. The method involves introduction into umbilical cord and placental stem cells of RNA with at least one sequence which ensures the transition of cells to the pluripotent state. The method enables to effectively prepare pluripotent stem cells from the cells of mammalian placenta and umbilical cord which have not yet acquired somatic mutations, which reduces the risk of oncogenesis and other adverse effects of reprogramming.

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Номер записи: 7
07-06-2012 дата публикации

Compositions and methods for promoting beta cell maturity

Номер: US20120141436A1
Автор: Arun Sharma, Cristina Aguayo-Mazzucato, Susan Bonner-Weir
Принадлежит: Joslin Diabetes Center Inc

Compositions and methods for providing an enriched population of mature, glucose-responsive insulin secreting cells, and for modulating insulin expression, activity and secretion in a subject.

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Номер записи: 8
07-06-2012 дата публикации

Method for inducing differentiation into epithelial progenitor cell/stem cell population and corneal epithelial cell population from induced pluripotent stem cells

Номер: US20120142103A1
Автор: Keisuke Okita, Kohji Nishida, Miharu Sakurai, Ryuhei Hayashi, Shinya Yamanaka, Tomofumi Kageyama
Принадлежит: KYOTO UNIVERSITY, Tohoku University NUC

The present invention relates to: a method for inducing differentiation into an epithelial progenitor cell/stem cell population or a corneal epithelial cell population by culturing, under particular conditions, induced pluripotent stem cells induced from mammalian somatic cells or undifferentiated stem cells; an epithelial progenitor cell/stem cell population or a corneal epithelial cell population obtained by the method; and a cell preparation for the treatment of epithelial disease and a cell sheet, which are prepared using these cell populations.

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Номер записи: 9
26-07-2012 дата публикации

Methods for obtaining hepatocytes, hepatic endoderm cells and hepatic progenitor cells by induced differentiation

Номер: US20120190059A1
Автор: Dongxin Zhao, Hongkui Deng, Mingxiao Ding, SONG Chen, Zhihua Song
Принадлежит: Beijing Huayuanbochuang Technology Co Ltd

The present invention discloses a method for inducing the differentiation of embryonic stem cells (ESC) or induced pluripotent stem cells (iPS cells) into hepatocytes, a method for inducing the differentiation of embryonic stem cells or induced pluripotent stem cells into hepatic endoderm cells, and a method for inducing the differentiation of embryonic stem cells (ESC) or induced pluripotent stem cells into hepatic progenitor cells. The present invention also provides the hepatocytes, hepatic endoderm cells and hepatic progenitor cells obtained by above methods, and the uses of these cells.

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Номер записи: 10
26-07-2012 дата публикации

Differentiation of Pluripotent Stem Cells

Номер: US20120190111A1
Автор: Christine Parmenter, Janet Davis, Jiajian Liu, Pascal Ghislain André Bonnet
Принадлежит: Janssen Biotech Inc

The present invention is directed to methods to differentiate pluripotent stem cells. In particular, the present invention is directed to methods and compositions to differentiate pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage comprising culturing the pluripotent stem cells in medium comprising a sufficient amount of GDF-8 to cause the differentiation of the pluripotent stem cells into cells expressing markers characteristic of the definitive endoderm lineage.

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Номер записи: 11
16-08-2012 дата публикации

Adipose-derived stem cells and lattices

Номер: US20120208274A1
Автор: Adam J. Katz, Hermann Peter Lorenz, J. William Futrell, Marc H. Hedrick, Min Zhu, Patricia Zuk, Peter H. Ashjian, Prosper Benhaim, Ramon Llull
Принадлежит: Individual

The present invention provides adipose-derived stem cells (ADSCs), adipose-derived stem cell-enriched fractions (ADSC-EF) and adipose-derived lattices, alone and combined with the ADSCs of the invention. In one aspect, the present invention provides an ADSC substantially free of adipocytes and red blood cells and clonal populations of connective tissue stem cells. The ADSCs can be employed, alone or within biologically-compatible compositions, to generate differentiated tissues and structures, both in vivo and in vitro. Additionally, the ADSCs can be expanded and cultured to produce molecules such as hormones, and to provide conditioned culture media for supporting the growth and expansion of other cell populations. In another aspect, the present invention provides a adipose-derived lattice substantially devoid of cells, which includes extracellular matrix material from adipose tissue. The lattice can be used as a substrate to facilitate the growth and differentiation of cells, whether in vivo or in vitro, into anlagen or even mature tissues or structures.

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Номер записи: 12
23-08-2012 дата публикации

Cardiomyocytes and methods of producing and purifying cardiomyocytes

Номер: US20120213748A1
Автор: Gabriel Nistor
Принадлежит: Individual

The invention provides methods for producing a culture of cardiomyocytes and cultures of cardiomyocytes. Exemplary methods of producing and cultures of cardiomyocytes include a population of cells including cells having spontaneous and periodic electrical activity, and/or including nodal, sino-atrial or pacemaker cells; immature cardiomyocytes (cardiomyoblasts); mature contractile cardiomyocytes; or a mixed population of two or more of such cells.

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Номер записи: 13
04-10-2012 дата публикации

Methods of generating a tendon tissue

Номер: US20120253463A1
Автор: Joseph Itskovitz-Eldor, Shahar Cohen
Принадлежит: Technion Research and Development Foundation Ltd

Methods of generating and expanding proliferative, multipotent connective tissue progenitor cells from adult stem cells are provided. Also provided are methods of generating functional tendon grafts in vitro and bone, cartilage and connective tissues in vivo using the isolated cell preparation of connective tissue progenitor cells.

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Номер записи: 14
29-11-2012 дата публикации

Technologies, Methods, and Products of Small Molecule Directed Tissue and Organ Regeneration from Human Pluripotent Stem Cells

Номер: US20120301437A1
Автор: Xuejun Huang Parsons
Принадлежит: SAN DIEGO REGENERATIVE MEDICINE INST

Pluripotent human embryonic stem cells (hESCs) hold great potential for restoring tissue and organ function, which has been hindered by inefficiency and instability of generating desired cell types through multi-lineage differentiation. This instant invention is based on the discovery that pluripotent hESCs maintained under defined culture conditions can be uniformly converted into a specific lineage by small molecule induction. Retinoic acid induces specification of neuroectoderm direct from the pluripotent state of hESCs and triggers progression to neuronal progenitors and neurons efficiently. Similarly, nicotinamide induces specification of cardiomesoderm direct from the pluripotent state of hESCs and triggers progression to cardiac precursors and cardiomyocytes efficiently. This technology provides a large supply of clinically-suitable human neuronal or cardiac therapeutic products for CNS or myocardium repair. This invention enables well-controlled efficient induction of pluripotent hESCs exclusively to a specific clinically-relevant lineage for tissue and organ engineering and regeneration, cell-based therapy, and drug discovery.

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Номер записи: 15
03-01-2013 дата публикации

Multipotent adult stem cell population

Номер: US20130004464A1
Автор: Bernardo Nadal-Ginard
Принадлежит: Individual

The present invention relates to the identification, isolation, expansion and characterization of a specific type of adult stem cell. These adult stem cells are characterised in that they naturally express many of the markers of totipotency, which have hitherto generally been limited to embryonic cell populations. The cells of the invention display an unprecedented capacity for multipotency; they are able to differentiate into cell types of mesodermal, endodermal and ectodermal origin. These adult stem cells may be used as therapeutic agents including, without limitation, for the regeneration of tissue, particularly for regeneration of damaged cardiac tissue, such as myocardium.

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Номер записи: 16
17-01-2013 дата публикации

Lineage-Restricted Neuronal Precursors

Номер: US20130017179A1
Автор: Anjali J. Kalyani, Mahendra S. Rao, Margot Mayer-Proschel
Принадлежит: University of Utah Research Foundation UURF

A cell population has been identified and isolated that can differentiate into multiple neuronal phenotypes, but cannot differentiate into glial phenotypes. This mammalian CNS neuron-restricted cell expresses highly polysialated or embryonic neural cell adhesion molecule (E-NCAM) and is morphologically distinct from neuroepithelial stem cells (NEP cells) and spinal glial progenitors derived from embryonic day 10.5 spinal cord. Methods for isolating these cells and uses thereof are also disclosed.

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Номер записи: 17
24-01-2013 дата публикации

Multipotent adult stem cell population

Номер: US20130023046A1
Автор: Bernardo Nadal Ginard
Принадлежит: Individual

The present invention relates to the discovery of a population of non-germ adult stem cells that can be found in tissue from non-embryonic mammals, including at least mouse, rat, pig and human. These adult stem cells, which are present within the post-natal individual at all ages from infancy to senescence have a phenotype and developmental potential that is different from stem cell types, embryonic and adult, that have so far been described.

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Номер записи: 18
31-01-2013 дата публикации

Method for hepatic differentiation of definitive endoderm cells

Номер: US20130031645A1
Автор: Anne Weber-Benarous, Ludovic Vallier, Thomas Touboul
Принадлежит: CAMBRIDGE ENTERPRISE LTD, Institut National de la Sante et de la Recherche Medicale INSERM

The present invention relates to a method for obtaining a population of hepatic progenitor cells, said method comprising a step of culturing definitive endoderm cells with a culture medium stimulating hepatic specification. In a particular embodiment, such culture medium stimulating hepatic specification comprises a retinoic acid receptor (RAR) agonist, an FGF family growth factor and an inhibitor of the activin signaling pathway.

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Номер записи: 19
07-03-2013 дата публикации

Isolated populations of adult renal cells and methods of isolating and using same

Номер: US20130059325A1
Автор: Benjamin Dekel
Принадлежит: Tel Hashomer Medical Research Infrastructure and Services Ltd

A method of generating a nephrospheroid is disclosed. The method comprises culturing human adult kidney cells in a culture medium under non-adherent conditions. Uses thereof and other renal cell populations are also disclosed.

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Номер записи: 20
28-03-2013 дата публикации

Scaffold-based organotypic culture for the long-term cultivation of human epidermal stem cells

Номер: US20130078666A1
Автор: Hans-Juergen Stark, Karsten Boehnke, Norbert Fusenig, Petra Boukamp
Принадлежит: Deutsches Krebsforschungszentrum DKFZ, Landesstiftung Baden Wuerttemberg gGmbH

The present invention relates to organotypic cultures of epidermal cells and the use thereof for the screening of pharmaceutical and cosmetic agents. Specifically, means for the improvement of the long-term stability of such cultures are disclosed. Thus, the present invention contemplates a skin equivalent comprising (a) a dermal equivalent comprising a matrix comprising nonwoven viscose fabric and fibroblasts and (b) keratinocytes. Moreover, the present invention contemplates a method for manufacturing the skin equivalent and a method for screening agents capable of influencing skin, such as a therapeutic or cosmetic agent.

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Номер записи: 21
02-05-2013 дата публикации

Method for obtaining pancreatic endocrine cells from adipose tissue-origin cells

Номер: US20130109092A1
Автор: Akifumi Matsuyama, Hiroshi Komoda, Yoshiki Sawa, Yuzuru Kanakura
Принадлежит: Osaka University NUC

A method of obtaining pancreatic endocrine cells from cells originating in an adipose tissue characterized by comprising culturing the adipose tissue-origin cells; the pancreatic endocrine cells that can be obtained thereby; a method of treating or preventing a disease caused by the hypofunction in pancreatic endocrine cells wherein the above-described pancreatic endocrine cells are used; a method of screening a substance capable of promoting or inhibiting the differentiation into pancreatic endocrine cells characterized by comprising adding a candidate substance to a medium in the course of culturing adipose tissue-origin cells to obtain the pancreatic endocrine cells; and so on.

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Номер записи: 22
09-05-2013 дата публикации

Formation of neuromuscular junctions in a defined system

Номер: US20130115694A1
Автор: James Hickman, Xiufang Guo
Принадлежит: University of Central Florida Research Foundation Inc UCFRF

A method for forming neuromuscular junctions includes forming functional neuromuscular junctions between motoneurons and muscle cells by co-culturing one or more human motoneurons and one or more human muscle cells in a substantially serum-free medium. A synthetic mammalian neuromuscular junction includes a human motoneuron functionally linked to a human muscle cell in a substantially serum-free medium. An artificial substrate may be used to support the one or more neuromuscular junctions.

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Номер записи: 23
27-06-2013 дата публикации

Cell compositions derived from dedifferentiated reprogrammed cells

Номер: US20130164787A1
Автор: Alan D. Agulnick, Allan Robins, Olivia Kelly, Thomas Schultz, Yuki Ohi
Принадлежит: Viacyte Inc

Disclosed herein are cell culture compositions, for example, pancreatic cell culture compositions, derived from dedifferentiated human reprogrammed pluripotent stem cells, such as induced pluripotent stem (iPS) cells, and methods for producing and using such cell culture compositions.

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Номер записи: 24
15-08-2013 дата публикации

Method of producing pancreatic hormone-producing cells

Номер: US20130210060A1
Автор: Masaki Hosoya, Masanobu Shoji
Принадлежит: Takeda Pharmaceutical Co Ltd

Disclosed is a production method of pancreatic hormone-producing cells in a form that mimics the pancreatogenesis, the method comprising subjecting stem cells to the following steps: (1) cultivating stem cells in a medium containing a Rho kinase inhibitor, (2) cultivating the cells obtained in (1) in a medium containing a GSK3 inhibitor, (3) cultivating the cells obtained in (2) in a medium containing GSK3 inhibitor and an activator of activin receptor-like kinase-4,7, (4) forming a cell mass from the cells obtained in (3), and cultivating the cell mass in a suspension state in a medium, (5) cultivating the cells obtained in (4) in a medium containing a retinoic acid receptor agonist, an inhibitor of AMP-activated protein kinase and/or activin receptor-like kinase-2,3,6, an inhibitor of activin receptor-like kinase-4,5,7 and a cell growth factor, and (6) cultivating the cells obtained in (5).

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Номер записи: 25
03-10-2013 дата публикации

Method of inducing differentiation of human pluripotent stem cell into hepatic progenitor cell

Номер: US20130260458A1
Автор: Minoru Tomizawa
Принадлежит: Chiba University NUC

The present invention relates to a differentiation inducing method comprising: introducing, into human induced pluripotent stem cells, a combination of genes of transcription factors which are possessed by fetal and adult hepatic cells, but are not possessed by human induced pluripotent stem cells; and adhering the human induced pluripotent stem cells to a substrate for monolayer culture in a medium containing a combination of growth-promoting agents for proliferation and differentiation, thereby enabling induction of the differentiation of the human induced pluripotent stem cells in large amounts in a short term, a hepatic progenitor cell produced by the method, and a cell composition for transplantation into the liver comprising the cell. The transcription factors include FOXA2, GATA4, HEX and C/EBPα, and the growth-promoting agents include oncostatin M, an epidermal growth factor, retinoic acid, dexamethasone, insulin, transferrin and a selenite ion.

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Номер записи: 26
17-10-2013 дата публикации

Serum-free media and their uses for chondrocyte expansion

Номер: US20130273010A1
Автор: Barbara Seymour, Stephen Duguay
Принадлежит: Genzyme Corp

The present invention provides defined serum-free cell culture media useful in culturing fibroblasts, especially articular chondrocytes, that avoid problems inherent in the use of serum-containing media. The defined media comprise platelet-derived growth factor (PDGF), chemically defined lipids, oncostatin M (OSM), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), or combinations of these compounds. In another aspect, the present invention also provides tissue culture methods that comprise incubating chondrocytes in the defined serum-free media. The methods enhance attachment and proliferative expansion of chondrocytes seeded at low density while maintaining their redifferentiation potential.

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Номер записи: 27
17-10-2013 дата публикации

Insulin producing cells derived from pluripotent stem cells

Номер: US20130273013A1
Автор: Alon Levy, Arik Hasson, Guy Slutsky, Judith Chebath, Michal Izrael, Michel Revel, MOLAKANDOV Kfir, Rosalia Kaufman
Принадлежит: KADIMASTEM Ltd

A method of generating islet cells from pluripotent stem cells is disclosed. The method comprises: (a) culturing the pluripotent stem cells in a differentiation medium so as to differentiate the pluripotent stem cells into endoderm cells; and (b) culturing the endoderm cells in a medium comprising at least one growth factor, a cAMP inducer and retinoic acid (RA), said at least one growth factor being selected from the group consisting of FGF10, bFGF and FGF7 so as to generate further differentiated cells; and (c) culturing the further differentiated cells in a medium comprising a maturation factor selected from the group consisting of nicotinamide, GLP-1 and exendin 4, thereby generating islet cells from pluripotent stem cells. Further methods of generating islet cells are also disclosed, isolated cell populations comprising same and uses thereof.

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Номер записи: 28
14-11-2013 дата публикации

Modalities for the treatment of degenerative diseases of the retina

Номер: US20130302426A1
Автор: Irina V. Klimanskaya, Robert Lanza
Принадлежит: Advanced Cell Technology Inc

This invention relates to methods for improved cell-based therapies for retinal degeneration and for differentiating human embryonic stem cells and human embryo-derived into retinal pigment epithelium (RPE) cells and other retinal progenitor cells.

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Номер записи: 29
28-11-2013 дата публикации

Method for stem cell differentiation in vivo by delivery of morphogenes with mesoporous silica and corresponding pharmceutical active ingredients

Номер: US20130315962A1
Автор: Alfonso E. Garcia-Bennett, Elena Nickolaevna Kozlova
Принадлежит: Nanologica AB

A pharmaceutical active ingredient for cell differentiation to alleviate cell and cell-related deficiencies in mammals comprising porous silica containing a releasable agent capable of contributing to a cell environment conducive for stem cell differentiation in co-implanted stem cells and/or in endogenous stem cells.

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Номер записи: 30
13-02-2014 дата публикации

Methods of culturing cells in a medium comprising transforming growth factor beta 1 and basic fibroblast growth factor

Номер: US20140045266A1
Автор: Joseph Itskovitz-Eldor, Michal Amit
Принадлежит: Technion Research and Development Foundation Ltd

The present invention is of methods of establishing and propagating human embryonic stem cell lines using feeder cells-free, xeno-free culture systems and stem cells which are capable of being maintained in an undifferentiated, pluripotent and proliferative state in culture which is free of xeno contaminants and feeder cells.

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Номер записи: 31
20-02-2014 дата публикации

Compositions Comprising Human Embryonic Stem Cells and Their Derivatives, Methods of Use, and Methods of Preparation

Номер: US20140051110A1
Автор: Geeta Shroff
Принадлежит: Individual

The present invention relates to a pharmaceutical composition comprising of preparations of human embryonic stem (hES) cells and their derivatives and methods for their transplantation into the human body, wherein transplantation results in the clinical reversal of symptoms, cure, stabilization or arrest of degeneration of a wide variety of presently incurable and terminal medical conditions, diseases and disorders. The invention further relates to novel processes of preparing novel stem cell lines which are free of animal products, feeder cells, growth factors, leukaemia inhibitory factor, supplementary mineral combinations, amino acid supplements, vitamin supplements, fibroblast growth factor, membrane associated steel factor, soluble steel factor and conditioned media. This invention further relates to the isolation, culture, maintenance, expansion, differentiation, storage, and preservation of such stem cells.

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Номер записи: 32
27-02-2014 дата публикации

Compositions Comprising Human Embryonic Stem Cells and Their Derivatives, Methods of Use, and Methods of Preparation

Номер: US20140057350A1
Автор: Geeta Shroff
Принадлежит: Individual

The present invention relates to a pharmaceutical composition comprising of preparations of human embryonic stem (hES) cells and their derivatives and methods for their transplantation into the human body, wherein transplantation results in the clinical reversal of symptoms, cure, stabilization or arrest of degeneration of a wide variety of presently incurable and terminal medical conditions, diseases and disorders. The invention further relates to novel processes of preparing novel stem cell lines which are free of animal products, feeder cells, growth factors, leukaemia inhibitory factor, supplementary mineral combinations, amino acid supplements, vitamin supplements, fibroblast growth factor, membrane associated steel factor, soluble steel factor and conditioned media. This invention further relates to the isolation, culture, maintenance, expansion, differentiation, storage, and preservation of such stem cells.

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Номер записи: 33
03-04-2014 дата публикации

Production of dentin, cementum and enamel by cells

Номер: US20140093481A1
Автор: Jeremy J. Mao, Mo Chen
Принадлежит: Columbia University of New York

One aspect provides a method of forming a mineralized material by co-culturing a epithelial cell, such as ameloblasts, and mesenchymal cells, such as osteoblasts or odontoblasts, in a mineral-stimulating medium. Another aspect provides matrix seeded with epithelial cells and mesenchymal cells and infused with a mineral-stimulating medium capable of forming a mineralized material in the matrix. Methods of manufacturing such compositions and methods of treating mineralization-related conditions are also provided.

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Номер записи: 34
05-01-2017 дата публикации

Modulation of Stem Cell and Progenitor Cell Differentiation, Assays, And Uses Thereof

Номер: US20170000779A1
Автор: David Stirling, Kyle W.H. Chan, Laure A. Moutouh-De Parseval, Robert J. Hariri
Принадлежит: Anthrogenesis Corp, Celgene Corp, Signal Pharmaceuticals LLC

The present invention relates to methods of modulating mammalian stem cell and progenitor cell differentiation. The methods of the invention can be employed to regulate and control the differentiation and maturation of mammalian, particularly human stem cells along specific cell and tissue lineages. The methods of the invention relate to the use of certain small organic molecules to modulate the differentiation of stem or progenitor cell populations along specific cell and tissue lineages, and in particular, to the differentiation of embryonic-like stem cells originating from a postpartum placenta or for the differentiation of early progenitor cells to a granulocytic lineage. Finally, the invention relates to the use of such differentiated stem or progenitor cells in transplantation and other medical treatments.

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Номер записи: 35
04-01-2018 дата публикации

Induced Hepatocytes and Uses Thereof

Номер: US20180000868A1
Автор: LEE Jau-Nan, LEE Tony Tung-Yin, LEE Yuta, TSAI Eing-Mei
Принадлежит:

Disclosed herein are induced hepatocytes from a trophoblast stem cell, methods for inducing the cells, and compositions thereof. Also disclosed herein are methods of treating a disease or disorder (e.g., liver-associated) by utilizing an induced hepatocyte disclosed herein. 189-. (canceled)90. An isolated human hepatocyte , wherein the isolated human hepatocyte expresses human leukocyte antigen G (HLA-G) and human cytoplasmic marker stem 121 (stem 121).91. The isolated human hepatocyte of claim 90 , wherein the isolated human hepatocyte is a human hepatic progenitor cell.92. The isolated human hepatocyte of claim 90 , wherein the isolated human hepatocyte further expresses one or more biomarkers selected from the group consisting of CXCR4 claim 90 , FOXA2 claim 90 , SOX17 claim 90 , HHEX claim 90 , TTR claim 90 , ALB claim 90 , TAT claim 90 , CYP7A1 claim 90 , BSEP claim 90 , SERPINA1 claim 90 , G6PC claim 90 , ABCC2 claim 90 , C/EBPβ claim 90 , HNF1α claim 90 , HNF4α claim 90 , and any combination thereof.93. The isolated human hepatocyte of claim 90 , wherein the isolated human hepatocyte further expresses TGFβ1 claim 90 , fibronectin claim 90 , or collagen IV in extracellular matrix (ECM).94. The isolated human hepatocyte of claim 90 , wherein the isolated human hepatocyte recruits CD4Foxp3 Treg cells.95. The isolated human hepatocyte of claim 90 , wherein the isolated human hepatocytes form tissue of a 3-dimensional structure.96. The isolated human hepatocyte of claim 90 , wherein the isolated human hepatocytes cluster or aggregate.97. The isolated human hepatocyte of claim 90 , wherein the isolated human hepatocytes form a crescent cell mass.98. The isolated human hepatocyte of claim 90 , wherein the isolated human hepatocyte further expresses one or more markers selected from the group consisting of TGFβ1 claim 90 , C-kit claim 90 , CK19 claim 90 , CK18 claim 90 , ALB claim 90 , α-AFP claim 90 , betatrophin claim 90 , ADH1 claim 90 , APOF claim 90 , CPS1 claim ...

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Номер записи: 36
07-01-2016 дата публикации

Bioengineered Liver Constructs And Methods Relating Thereto

Номер: US20160002602A1
Автор: Almeida-Porada Maria Graca, Baptista Pedro Miguel A.M., Soker Shay
Принадлежит:

An in vitro liver organoid is provided along with methods of making and using the organoid. The liver organoid can be manipulated to have either immature or mature characteristics. Some manipulations generate a liver organoid that supports expansion and/or differentiation of hematopoietic stem cells. 1. A liver organoid comprising:(a) a bioscaffold derived from a decellularized donor subject liver comprising a native extracellular matrix (ECM) and native vascular channels; and(b) liver cells having predominately fetal characteristics.2. A liver organoid comprising:(a) a bioscaffold derived from a decellularized donor subject liver comprising a native extracellular matrix (ECM) and native vascular channels; and(b) liver cells having adult characteristics.3. A method of generating a liver organoid comprising the steps of:(a) providing a bioscaffold derived from a decellularized donor subject liver comprising a native extracellular matrix (ECM) and native vascular channels;(b) seeding the bioscaffold with liver cells; and(c) culturing the liver cells with culture medium containing at least one growth factor to generate a liver organoid comprising differentiated liver cells over time.4. The liver organoid of claim 1 , wherein the-liver cells form at least one of a micro-environment niche that supports hematopoietic stem cell (HSC) expansion or a micro-environment niche that supports HSC differentiation.56-. (canceled)7. The liver organoid of claim 1 , wherein the liver cells comprise at least one of liver progenitor cells claim 1 , hepatoblasts claim 1 , vascular cells claim 1 , cholangiocytes claim 1 , or stromal cells.8. The liver organoid of claim 7 , wherein the vascular cells comprise at least one of liver endothelial cells claim 7 , liver sinusodial cells claim 7 , vascular smooth muscle cells claim 7 , or pericytes.9. The liver organoid of claim 7 , wherein the hepatoblasts comprise at least one of fetal liver hepatoblasts claim 7 , hepatoblasts derived from ...

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Номер записи: 37
02-01-2020 дата публикации

METHOD FOR INDUCING TRANS-DIFFERENTIATION OF CARDIOMYOCYTES BASED ON EXOSOME

Номер: US20200002677A1
Автор: KIM Hyosuk, KIM Sun Hwa, KWON Ick Chan, YANG Yoosoo
Принадлежит: KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

The present invention relates to a method for inducing trans-differentiation of cardiomyocytes based on exosome, and more particularly, to a method for inducing trans-differentiation of a fibroblast into a cardiomyocyte, comprising the steps of: isolating exosomes in a culture medium during a process of differentiating a stem cell into the cardiomyocyte; culturing a fibroblast in a cardiomyocyte reprogramming medium containing the isolated exosomes; and culturing the fibroblast cultured in a cardiomyocyte differentiation medium containing the isolated exosomes. 1. A method of inducing trans-differentiation a fibroblast to a cardiomyocyte , the method comprising:isolating exosomes in a culture medium during a process of differentiating a stem cell into the cardiomyocyte;culturing a fibroblast in a cardiomyocyte reprogramming medium containing the isolated exosomes; andculturing the fibroblast cultured in a cardiomyocyte differentiation medium containing the isolated exosomes.2. The method according to claim 1 , wherein the exosomes are prepared by mixing a first exosome isolated during a mesoderm induction process and a second exosome isolated during a cardiac specification and maturation process.3. The method according to claim 2 , wherein mixing ratio of the first exosome and the second exosome is from 1:19 to 19:1.4. The method according to claim 1 , wherein the cardiomyocyte reprogramming medium comprises 2 to 7 wt % of KnockOut Serum Replacement claim 1 , 10 to 17 wt % of embryonic stem cell fetal calf serum (ES-FBS) claim 1 , 0.1 to 2 wt % of N2 claim 1 , 1 to 3 wt % of B-27 claim 1 , 0.5 to 2 wt % of Glutamax claim 1 , 0.5 to 2 wt % of nonessential amino acid (NEAA) claim 1 , 0.05 to 0.2 mM of β-mercaptoethanol claim 1 , and 20 to 70 μg/ml of ascorbic acid.5. The method according to claim 1 , the cardiomyocyte differentiation medium comprises 12 to 20 wt % of fetal bovine serum claim 1 , 20 to 70 μg/ml of ascorbic acid claim 1 , 0.5 to 2 μg/ml of insulin claim ...

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Номер записи: 38
02-01-2020 дата публикации

CRUSHED STEM CELL EXTRACT (SHELLED STEM CELL) MANUFACTURING METHOD USING MASS CULTURE MEDIUM COMPOSITION METHOD AND CONSTITUENT 3-LOW EXTRACTING METHOD AND A TREATING COMPOSITION FOR ANTI-INFLAMMATORY AND A TREATING COMPOSITION FOR CELL REGENERATION

Номер: US20200002678A1
Автор: Kim Young-Sil, LEE Hye-Jin, Park Jung-Eun
Принадлежит: Tiara Stem Cell Institute

Disclosed is a method of manufacturing a medium composition for cell culture, and a method of manufacturing a crushed stem cell extract using a method of manufacturing a medium composition for cell culture and a 3-low extracting method of active ingredients of a stem cell. The medium composition for cell culture includes a basal medium; a hyaluronic acid; and an additive composition. According to an embodiment, when active ingredients of a stem cell are extracted, a stem cell is crushed at a 3-low circumstance of low temperature, low pressure, a hypotonic circumstance. 1. A method of manufacturing a medium composition for cell culture , comprising:a basal medium;a hyaluronic acid; andan additive composition.2. The method according to claim 1 , wherein the additive composition comprises at least one of glycine claim 1 , histidine claim 1 , isoleucine claim 1 , methionine claim 1 , phenylalanine claim 1 , proline claim 1 , hydroxyproline claim 1 , serine claim 1 , threonine claim 1 , tryptophan claim 1 , tyrosine claim 1 , valine claim 1 , bFGF claim 1 , EGF claim 1 , VEGF claim 1 , KGF claim 1 , HGF claim 1 , TGF claim 1 , vitamin C claim 1 , vitamin B1 claim 1 , vitamin B12 claim 1 , vitamin E claim 1 , selenium claim 1 , and transferrin.3. The method according to claim 1 , wherein the basal medium comprises one of DMEM (Dulbecco's Modified Eagle's Medium) claim 1 , MEM (Minimal Essential Medium) claim 1 , BME (Basal Medium Eagle) claim 1 , RPMI 1640 claim 1 , F-10 claim 1 , F12 claim 1 , DMEM-F12 claim 1 , α-MEM (α-Minimal Essential Medium) claim 1 , G-MEM (Glasgow's Minimal Essential Medium) claim 1 , IMDM (Iscove's Modified Dulbecco's Medium) claim 1 , MacCoy's 5A medium claim 1 , AmnioMax claim 1 , AminoMax II complete Medium claim 1 , Chang's Medium MesemCult-XF Medium.4. The method according to claim 2 , wherein claim 2 , in the additive composition claim 2 ,a concentration of the hyaluronic acid to the medium composition is 10 μg/Ml,a concentration of the ...

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Номер записи: 39
07-01-2021 дата публикации

Compositions and Methods for Efficient Amplification of Retinal Progenitors Cells

Номер: US20210002607A1
Автор: Goureau Olivier, Reichman Sacha, Sahel Jose-Alain
Принадлежит:

The disclosure pertains to a defined cell culture medium for the expansion of human retinal progenitors, comprising or consisting of a nutrient medium, a SHH-pathway activator and a GSK3 inhibitor. To the use of the defined cell culture medium for the expansion of retinal progenitors, as well as to an in vitro method for expanding retinal progenitors, comprising: (i) placing a culture of human retinal progenitors in a defined cell culture medium as defined in claims to ; and (ii) culturing the cells in said defined cell culture medium. 1. A defined cell culture medium for the expansion of human retinal progenitors , comprising a nutrient medium , a SHH-pathway activator and a GSK3 inhibitor , and said defined cell culture medium is devoid of DAPT.2. The defined cell culture medium according to claim 1 , further comprising FGF2 and/or EGF and/or ATP.3. The defined cell culture medium according to claim 1 , further comprising a pro-neural supplement claim 1 , wherein said pro-neural supplement comprises a mixture of insulin and transferrin.4. The defined cell culture medium according to claim 3 , wherein the pro-neural supplement is chosen among the pro-neural supplement consisting of:a mixture of BSA, transferrin, insulin, progesterone, putrescine, sodium selenite, biotine, 1-carnitine, cortisone or hydrocortisone, ethanolamine, d(+)galactose, glutathione (reduced), linolenic acid, linoleic acid, retinyl acetate, selenium, T3 (triodo-1-thryonine), dl-α-tocopherol (vitamin E), dl-α-tocopherol acetate, catalase and superoxide dismutase;a mixture of transferrin, insulin, progesterone, putrescine and sodium selenite;a mixture of BSA, transferrin and insulin; ora mixture of transferrin, insulin, sodium selenite, FGF2 and EGF.5. The defined cell culture medium according to claim 1 , wherein the SHH-pathway activator is selected from the list consisting of purmorphamine claim 1 , SHH claim 1 , smoothened agonist claim 1 , Hh-Ag 1.5 or zinc finger protein Gli-2.6. The ...

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Номер записи: 40
07-01-2021 дата публикации

METHODS AND COMPOSITIONS FOR PREPARING CARDIOMYOCYTES FROM STEM CELLS AND USE THEREOF

Номер: US20210002614A1
Автор: Ma Yue
Принадлежит: Institute of Biophysics, Chinese Academy of Sciences

The present invention discloses novel compositions and methods for enhancing cardiac differentiation efficiency of stem cells or promoting ventricular and atrial cardiomyocytes formation from stem cells. The present invention also discloses the atrial and ventricular cardiomyocytes formed from the stem cells, and the uses of the cardiomyocytes for repairing cardiac injuries and screening for new medicaments for treating cardiac injuries. 177-. (canceled)78. A pharmaceutical composition for treating a cardiac injury or disorder , which pharmaceutical composition comprises an effective amount of a ventricular cardiomyocyte differentiated , in vitro , from a mesodermal cell in which the retinoic acid signaling pathway is inhibited by an exogenous agent to promote ventricular cardiomyocyte formation from the mesodermal cell.79. The pharmaceutical composition of claim 78 , wherein the mesodermal cell is differentiated from a pluripotent stem cell claim 78 , a totipotent stem cell claim 78 , a multipotent stem cell claim 78 , an oligopotent stem cell claim 78 , a unipotent stem cell claim 78 , an embryonic stem cell claim 78 , an induced pluripotent stem cell claim 78 , a fetal stem cell claim 78 , or an adult stem cell.80. The pharmaceutical composition of claim 78 , wherein the mesodermal cell is differentiated from a mammalian stem cell.81. The pharmaceutical composition of claim 78 , wherein the mesodermal cell is differentiated from a human stem cell claim 78 , a human embryonic stem cell claim 78 , or a human induced pluripotent stem cell.82. The pharmaceutical composition of claim 78 , wherein the mesodermal cell is generated by contacting a stem cell with basic fibroblast growth factor (bFGF) claim 78 , BMP 4 and/or activin A.83. The pharmaceutical composition of claim 78 , wherein the mesodermal cell is generated by contacting a stem cell with Wnt-3a claim 78 , Bio claim 78 , or CHIR99021.84. The pharmaceutical composition of claim 78 , wherein the mesodermal ...

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Номер записи: 41
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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Номер записи: 42
03-01-2019 дата публикации

COMPOSITIONS AND METHODS FOR THE GENERATION OF MELANOCYTES THROUGH DIRECT REPROGRAMMING

Номер: US20190002827A1
Автор: Xu Xiaowei, Yang Ruifeng
Принадлежит:

Compositions and methods for generating melanocytes through direct reprogramming are disclosed. Also disclosed are methods of use of such compositions for the treatment of vitiligo and other hypopigmentation disorders. In accordance with the present invention, a method for producing melanocytes suitable for use in human patients is provided. An exemplary method comprises providing cells capable of transdifferentiation into melanocytes, culturing said cells in a chemically defined culture medium, introducing at least two of microphthalmia-associated transcriptiokn factor (MITF), SRY-related HMG-box (SOX10) transcription factor and paired box-3 (PAX-3) transcription factor and paired box-3 (PAX-3) transcription factor, or nucleic acids encoding said transcription factors into said cells, wherein expression of said factors induces the cells to transdifferentiae into melanocytes expressing melanocyte markers TYR, DCT, S-100 and Melan-A. 1. A method for producing melanocytes comprising:a) providing cells capable of transdifferentiation into melanocytes;b) culturing said cells in a chemically defined culture medium;c) introducing at least two of microphthalmia-associated transcription factor (MITF), SRY-related HMG-box (SOX10) transcription factor and paired box-3 (PAX-3) transcription factor, or nucleic acids encoding said transcription factors into said cells, thereby inducing said cells to transdifferentiae into melanocytes expressing melanocyte markers TYR, DCT, S-100 and Melan-A; and, optionallyd) isolating said melanocytes.2. The method of claim 1 , wherein all three transcription factors are introduced and said cells are fibroblasts.3. The method of claim 1 , wherein said cells are mammalian in origin.4. The method of claim 3 , wherein said cells are human in origin.5. The method of claim 2 , wherein said cells are fetal or adult fibroblasts.6. (canceled)7. The method of claim 1 , wherein said transcription factors are encoded by one or more recombinant expression ...

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Номер записи: 43
03-01-2019 дата публикации

CELL MEDIUM FORMULATION FOR CELL STABILIZATION

Номер: US20190002831A1
Автор: Petcavich Robert John, Si Wongjong, Spangenberg Stephan, Yeh Ping, Zanella Fabian
Принадлежит:

A cell preservation medium, a cell recovery medium and a cell culture medium, and methods which employ the media, are provided. 1. A cell preservation medium comprising: cell hibernation medium and L-glutamine or an analog thereof , and one or more of ascorbic acid , albumin , or insulin.2. The medium of claim 1 , wherein the cell hibernation medium comprises Hibernate®E.3. The medium of claim 1 , wherein the analog comprises L-alanyl-L-glutamine dipeptide.4. The medium of claim 1 , wherein the concentration of the L-glutamine or the analog dipeptide is about 0.5 mM to about 4 mM or about 1 mM to about 2 mM or wherein the ascorbic acid is about 100 μg/mL to about 300 μg/mL or about 150 to about 200 mM or wherein the albumin is about 200 μg/mL to about 700 μg/mL or about 300 to about 400 mM or wherein the insulin is about 1 μg/mL to about 20 μg/mL or about 4 to about 6 mM.57-. (canceled)8. The medium of further comprising cells.9. The medium of wherein the cells are cardiomyocytes.10. (canceled)117. A cell recovery medium comprising: the cell preservation medium of any one of to claims 1 , and M199 claims 1 , DMEM claims 1 , glucose or other sugar based energy source claims 1 , glutamine or an analog thereof claims 1 , and one or more of ascorbic acid claims 1 , albumin claims 1 , or insulin claims 1 , wherein the cell recovery medium has about 45% to about 55% cell preservation medium claims 1 , wherein the cell recovery medium has about 10% to about 15% M199 and about 35% to about 40% DMEM.12. The medium of claim 11 , which comprises about 2 g/L to about 8 g/L or about 4 g/L to about 5 g/L glucose or other sugar.13. The medium of claim 11 , wherein the L-glutamine or analog in the cell recovery medium is about 0.5 mM to about 4 mM or about 1 mM to about 2 mM or wherein the ascorbic acid in the cell recovery medium is about 100 μg/mL to about 300 μg/mL or about 150 μg/mL to about 200 μg/mL or wherein the albumin in the cell recovery medium is about 200 μg/mL to ...

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Номер записи: 44
01-01-2015 дата публикации

Method for differentiating stem cells into neurons

Номер: US20150004701A1
Автор: Hee Hoon Yoon, Jung Keug Park, Soo Yeon Kim, Young Kwon Seo
Принадлежит: Industry Academic Cooperation Foundation of Dongguk University

The present invention relates to a method for differentiating stem cells into neurons, and is characterized in that stem cells are treated with a culture additive comprising lipoic acid, albumin, hydrocortisone, and insulin after culturing for differentiation into neurons. Since the neurons produced according to the method for producing neurons of the present invention express nestin, neuroD1, neuron-specific enolase (NSE), neurofilament (NF), tau, microtubule-associated protein 2 (MAP2), and doublecortin (DCX), just as normal mature neurons do, the neurons of the present invention can be effectively used in various therapeutic agents for neurons and as cell origins for an in vitro study system.

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Номер записи: 45
13-01-2022 дата публикации

OVARIAN FOLLICLE CELLS AND CONSTRUCTS FOR FERTILITY TREATMENT AND HORMONE REPLACEMENT THERAPY

Номер: US20220010270A1
Автор: Atala Anthony, Jackson John D., Sequeira Russel C., Sivanandane Sittadjody, Yoo James J.
Принадлежит:

A method of providing a culture of oogonia stem cells comprising oogonia stem cells is provided. The method may further include culturing the oogonia stem cells with granulosa and theca cells to differentiate the oogonia stem cells into oocytes. In some embodiments, the culturing comprises including the oogonia stem cells in an in vitro follicle construct or a microcapsule comprising said granulosa and theca cells. Further described herein is a method of forming a bioengineered follicle construct capable of releasing a mature oocyte. An in vitro fertilization method using the mature oocyte is also provided. 2. The method of claim 1 , wherein the ovary tissue is adult human ovary tissue.3. The method of claim 1 , wherein the separating is carried out with fluorescent-activated cell sorting (FASC) claim 1 , immunomagnetic bead sorting claim 1 , or magnetic activated cell sorting (MASC).4. The method of claim 1 , wherein said providing step comprises: isolating ovarian cells from the ovary tissue; and culture expanding the ovarian cells in a germ-line stem cell media.5. The method of claim 1 , further comprising a step of collecting ovarian cells that are not positive for either DDX4 or IFITM3 claim 1 , to provide a second population comprising cells that can differentiate into granulosa and theca cells.6. The method of claim 5 , wherein the method further comprises differentiating the cells of the second population into granulosa and/or theca cells.7. The method of claim 1 , further comprising culturing the oogonia stem cells with granulosa and theca cells claim 1 , to differentiate the oogonia stem cells into oocytes.8. The method of claim 7 , wherein the culturing comprises contacting the oogonia stem cells with a combination of retinoic acid claim 7 , follicle-stimulating hormone claim 7 , and estradiol.10. The in vitro follicle construct of claim 9 , wherein one claim 9 , two claim 9 , or all three of the live mammalian ovarian granulosa cells claim 9 , live ...

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Номер записи: 46
12-01-2017 дата публикации

Adoptive Cellular Therapy Using an Agonist of Retinoic Acid Receptor-Related Orphan Receptor Gamma & Related Therapeutic Methods

Номер: US20170007686A1
Автор: Aicher Thomas D., Celeste Laura Lee, Glick Gary D., HU XIAO, Liu Xikui, Taylor Clarke B., Toogood Peter L., Van Huis Chad A.
Принадлежит:

The invention relates to medical therapy using an agonist of the retinoic acid receptor-related orphan receptor gamma (RORγ) and provides adoptive cellular therapies using an agonist of RORγ, populations of lymphocyte cells that have been exposed to an agonist of RORγ, populations of dendritic cells that have been exposed to an agonist of RORγ, pharmaceutical compositions, and methods for enhancing therapeutic effects of lymphocyte cells and/or dendritic cells in a patient by administering an agonist of RORγ to a patient. 1. A method of delivering to a patient a RORγ agonist treated cell selected from the group consisting of a lymphocyte cell and dendritic cell , comprising administering to a patient in need thereof a pharmaceutical composition comprising said cell that has been exposed ex vivo to an agonist of RORγ.2. The method of claim 1 , further comprising culturing a cell selected from the group consisting of a lymphocyte cell and dendritic cell with an agonist of RORγ to provide the cell that has been exposed ex vivo to an agonist of RORγ.3. The method of claim 2 , wherein the culturing comprises exposing the cell to a cytokine.4. The method of claim 3 , wherein the cytokine is IL-1β claim 3 , IL-2 claim 3 , IL-6 claim 3 , IL-7 claim 3 , IL-10 claim 3 , IL-12 claim 3 , IL-15 claim 3 , IL-18 claim 3 , IL-21 claim 3 , IL-23 claim 3 , or transforming growth factor beta.5. The method of any one of - claim 3 , wherein the culturing comprises exposing the cell to an antigen associated with a medical disorder.6. The method of claim 5 , wherein the antigen comprises cancer tissue.7. The method of any one of - claim 5 , further comprising obtaining a lymphocyte cell or dendritic cell from said patient for use in the culturing step.8. The method of any one of - claim 5 , further comprising obtaining a lymphocyte cell or dendritic cell from a subject that produces cells allogenic to cells of the patient claim 5 , for use in the culturing step.9. The method of any one of ...

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Номер записи: 47
11-01-2018 дата публикации

METHODS FOR PRODUCTION OF PLATELETS FROM PLURIPOTENT STEM CELLS AND COMPOSITIONS THEREOF

Номер: US20180008640A1
Автор: Feng Qiang, Lanza Robert P., Lu Shi-Jiang
Принадлежит: Astellas Institute for Regenerative Medicine

Methods for production of platelets from pluripotent stem cells, such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are provided. These methods may be performed without forming embryoid bodies or clusters of pluripotent stem cells, and may be performed without the use of stromal inducer cells. Additionally, the yield and/or purity can be greater than has been reported for prior methods of producing platelets from pluripotent stem cells. Also provided are compositions and pharmaceutical preparations comprising platelets, preferably produced from pluripotent stem cells. 1. A pharmaceutical preparation that is suitable for use in a human patient comprising at least 10platelets , wherein the preparation is substantially free of leukocytes and wherein substantially all of the platelets are functional.2. The pharmaceutical preparation of that comprises 10-10platelets claim 1 , optionally 10 claim 1 , 10 claim 1 , 10 claim 1 , 10 claim 1 , 10 claim 1 , or 10platelets.3. The pharmaceutical preparation of claim 1 , wherein the platelets have one or more of the following attributes: a mean platelet volume range of 9.7-12.8 fL; a unimodal distribution of size in the preparation; and/or a lognormal platelet volume distribution wherein one standard deviation is less than 2 μm claim 1 , (less than 1.5 μm claim 1 , less than 1 μmor less than 0.5 μm.4. The pharmaceutical preparation of claim 1 , wherein the platelets are positive for at least one of the following markers: CD41a and CD42b.5. The pharmaceutical preparation of claim 1 , wherein the platelets are human platelets.6. The pharmaceutical preparation of claim 1 , wherein at least 50% claim 1 , 60% claim 1 , 70% claim 1 , 80% or 90% of the platelets are functional for at least 2 claim 1 , 3 or 4 days after storage at room temperature.745-. (canceled)46. A method for producing a pharmaceutical preparation comprising:differentiating megakaryocytes positive for CD41a and CD42b expression in a ...

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Номер записи: 48
08-01-2015 дата публикации

INTERVERTEBRAL DISC REPAIR COMPOSITIONS AND METHODS

Номер: US20150010501A1
Автор: Crawford Keith D., Gadboys Jeffrey A., Garvey John, Layton Pamela
Принадлежит:

The present invention provides compositions, methods and devices for treatment of degenerative disc disease or the repair of a disc in need of repair. The composition or the formulation includes freshly isolated or culture expanded ELA cells, which can be cyropreserved. The composition or a formulation also includes in various embodiments an ELA cell population that has been differentiated into cell types having at least one characteristic of human intervertebral disc cells, such as fibroblast cells, chondrocyte cells or notochordal cells. The composition or the formulation includes in certain embodiments either a population of ELA cells provided in conjunction with one or more biocompatible molecules, therapeutic agents, or agents that induce ELA stem cell differentiation. The ELA cells are obtained from fluid or tissue from live or cadaveric (cadaverous) donors. Treatment of a degenerative disc or a disc in need of repair includes in various embodiments one or more injections or implantations of the composition comprising the ELA cells within or in association with the disc in need of repair. 1. A formulation comprising: a preparation of ELA stem cells characterized by expression of one or more stem cell-specific transcription factors , and lacking detectible expression of one or more of the cell surface markers: CD13 , CD34 , CD44 , CD45 , CD90 , and MHC class I.2. The formulation according to further comprising at least one selected from: a pharmaceutically acceptable excipient claim 1 , a contrast agent claim 1 , an analgesic agent claim 1 , a radiographic agent claim 1 , a buffer claim 1 , a cryogenic agent claim 1 , and a therapeutic agent.3. (canceled)4. The formulation according to claim 2 , wherein the contrast agent comprises a perfluorate agent.5. (canceled)6. (canceled)7. The formulation according to claim 1 , further comprising at least one selected from the group of: a matrix claim 1 , a scaffold claim 1 , an implant claim 1 , a cadaveric tissue claim ...

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Номер записи: 49
08-01-2015 дата публикации

MAMMALIAN NEURAL PLATE BORDER STEM CELLS CAPABLE OF FORMING NEURAL TUBE AND NEURAL CREST CELL LINEAGES INCLUDING CENTRAL AND PERIPHERAL NEURONS

Номер: US20150010515A1
Автор: GLATZA Michael, REINHARDT Peter, SCHOELER Hans R., STERNECKERT Jared L.
Принадлежит:

The present invention relates to a method for producing mammalian neural plate border stem cells (NPBSCs), comprising: (a) differentiation of mammalian pluripotent stem cells by (a-i) culturing mammalian pluripotent stem cells in pluripotent stem cell medium for about 24 to about 96 hours, wherein the pluripotent stem cell medium comprises: (i) an inhibitor of the activin/TGF-β signalling pathway; (ii) an inhibitor of the BMP signalling pathway; (iii) an activator of the canonical WNT signalling pathway; and (iv) an activator of the Hedgehog signalling pathway; subsequently (a-ii) culturing the cells obtained in step (a-i) for about 24 to about 96 hours in a neural medium, wherein the neural medium comprises: (i) an inhibitor of the Activin/TGF-β signalling pathway; (ii) an inhibitor of the BMP signalling pathway; (iii) an activator of the canonical WNT signalling pathway; and (iv) an activator of the Hedgehog signalling pathway; subsequently (a-iii) culturing the cells obtained in step (a-ii) for about 24 to about 96 hours in a neural medium, wherein the neural medium comprises: (i) an activator of the canonical WNT signalling pathway; (ii) an activator of the Hedgehog signalling pathway; and (iii) an inhibitor of oxidation; and (b) plating the obtained differentiated mammalian pluripotent stem cells in NPBSCs expansion medium, wherein the NPBSCs expansion medium comprises (i) an activator of the canonical WNT signalling pathway; (ii) an activator of the Hedgehog signalling pathway; and (iii) an inhibitor of oxidation; and expanding the cells in the NPBSCs expansion medium for about 24 to about 96 hours; (c) splitting the cells obtained in (b) and further expanding the cells in the NPBSCs expansion medium; and (d) repeating step (c) at least two times. The present invention further relates to neural plate border stem cells obtainable by the method of the invention and the use of the cells of the invention in medicine. 1. A method for producing mammalian neural ...

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Номер записи: 50
12-01-2017 дата публикации

GUIDED DIFFERENTIATION OF INDUCED PLURIPOTENT STEM CELLS

Номер: US20170009210A1
Автор: El Khatib Moustafa M.A., IKEDA Yasuhiro
Принадлежит: Mayo Foundation for Medical Education and Research

This document provides methods and materials related to making and using differentiated induced pluripotent stem cells. For example, methods and materials for making differentiated induced pluripotent stem cells (e.g., insulin-producing cells) that do not form cancer cells within a mammal (e.g., a human), cells that underwent guided differentiation from induced pluripotent stem cells, compositions containing cells that underwent guided differentiation from induced pluripotent stem cells, and methods for using cells that underwent guided differentiation from induced pluripotent stem cells (e.g., methods for using such cells to treat diabetes or to repair cardiovascular tissue) are provided. 1. A population of differentiated cells obtained from induced pluripotent stem cells , wherein the cells of said population lack integrated viral nucleic acid encoding a stemness factor , wherein implantation of said population of differentiated cells into a mammal does not result in cancer cell formation , and wherein said cells were obtained using a culture comprising an enzyme.2. The population of differentiated cells of claim 1 , wherein said cells are human cells.3. The population of differentiated cells of claim 1 , wherein said cells lack exogenous nucleic acid.4. The population of differentiated cells of claim 1 , wherein said enzyme is trypsin.5. A method for obtaining a population of differentiated cells obtained from induced pluripotent stem cells claim 1 , wherein said method comprises:(a) exposing somatic cells to one or more non-integrating viral vectors that direct the expression of one or more stemness factors to produce induced pluripotent stem cells from said somatic cells, and(b) exposing said induced pluripotent stem cells to one or more differentiation factors in the presence of an enzyme to produce a population of cells more specialized than said induced pluripotent stem cells.6. The method of claim 5 , wherein said somatic cells are keratinocytes.7. The ...

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Номер записи: 51
27-01-2022 дата публикации

In vitro method of differentiating a human pluripotent stem cell population into a cardiomyocyte cell population

Номер: US20220025333A1
Автор: Ana Catarina Martins GRANDELA, Stefan Robbert BRAAM
Принадлежит: Ncardia Bv

The current invention relates to a method of differentiation of human pluripotent stem cells into a human stem-cell derived population of cardiomyocytes. The method comprises the use of specific combination of steps and compounds to induce and/or promote differentiation. The method also comprises steps directed to further maturation of the cardiomyocytes obtained with the method of the invention. Also provided are kits for use in a method of differentiation as well as cell populations obtainable with the method disclosed.

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Номер записи: 52
14-01-2016 дата публикации

Generation of Thymic Epithelial Progenitor Cells In Vitro

Номер: US20160010055A1
Автор: Anderson Mark Stuart, Hebrok Matthias, Parent Audrey
Принадлежит:

Methods for generating thymic epithelial progenitor (TEP) cells from pluripotent stem (PS) cells in vitro are provided. Compositions and systems of cell populations of TEP cells as well as cells formed during different stages of differentiation of PS cells into TEP cells are also disclosed. The methods, isolated in vitro cell populations, compositions, and systems disclosed provide functional TEP cells that mature into thymic epithelial cells in vivo. 1. A method for generating thymic epithelial progenitor (TEP) cells , the method comprising:culturing definitive endodermal (DE) cells obtained from pluripotent stem cells in a medium comprising an activator of retinoic acid receptor, an activator of bone morphogenetic protein (BMP) signaling, and an inhibitor of transforming growth factor-β (TGF-β) signaling.2. The method of claim 1 , wherein the DE cells are obtained from pluripotent stem cells by culturing pluripotent stem cells in a medium comprising a growth factor selected from the group consisting of Nodal claim 1 , Activin A claim 1 , and Activin B.3. The method of or claim 1 , wherein the method comprises:culturing anterior foregut endodermal (AFE) cells produced by said culturing of the DE cells, wherein said culturing of the AFE cells is in a medium comprising an activator of retinoic acid receptor, an activator of bone morphogenetic protein (BMP) signaling, and an inhibitor of transforming growth factor-β (TGF-β) signaling.4. The method of claim 3 , wherein the method comprises:culturing ventral pharyngeal endodermal (VPE) cells produced by said culturing of the AFE cells, wherein said culturing of the VPE cells is in a medium comprising an activator of retinoic acid receptor and an activator of bone morphogenetic protein (BMP) signaling.5. A method for generating thymic epithelial progenitor (TEP) cells claim 3 , the method comprising:culturing anterior foregut endodermal (AFE) cells obtained from pluripotent stem cells in a medium comprising an activator ...

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Номер записи: 53
11-01-2018 дата публикации

CELLS GENETICALLY MODIFIED TO COMPRISE PANCREATIC ISLET GLUCOKINASE AND USES THEREOF

Номер: US20180010104A1
Автор: Simpson Ann Margaret, Tao Chang
Принадлежит:

The present invention relates generally to a population of cells genetically modified to produce insulin in a glucose responsive manner and uses thereof. More particularly, the present invention relates to a population of cells genetically modified to produce insulin in response to physiologically relevant levels of glucose and uses thereof. The cells of the present invention are useful in a wide variety of applications, in particular in the context of therapeutic and prophylactic regimes directed to the treatment of diabetes and/or the amelioration of symptoms associated with diabetes, based on the transplantation of the cells of the present invention into mammals requiring treatment. Also facilitated is the design of in vitro based screening systems for testing the therapeutic effectiveness and/or toxicity of potential adjunctive treatment regimes. 1. (canceled)2. An isolated mammalian hepatocyte recombinantly expressing insulin protein , pancreatic islet glucokinase protein , and GLUT2 protein , and wherein the mammalian hepatocyte produces insulin when exposed to an extracellular glucose concentration from about 3 mM to about 8 mM.3. The mammalian hepatocyte of claim 2 , wherein the insulin protein is a human insulin protein claim 2 , the pancreatic islet glucokinase protein is a human pancreatic islet glucokinase claim 2 , and the GLUT2 protein is a human GLUT2 protein.4. The mammalian hepatocyte of claim 2 , wherein the pancreatic islet glucokinase has an amino acid sequence of SEQ ID NO: 2 or at least 90% identical to SEQ ID NO: 2.5. The mammalian hepatocyte of claim 2 , wherein the mammalian hepatocyte is a human hepatocyte.6. The mammalian hepatocyte of claim 2 , wherein the mammalian hepatocyte is a Huh7 cell.7. The mammalian hepatocyte of claim 2 , wherein the hepatocytes are autologous cells claim 2 , allogenic cells claim 2 , or combination thereof.8. The mammalian hepatocyte of claim 2 , wherein the hepatocytes are encapsulated.9. An isolated mammalian ...

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Номер записи: 54
14-01-2021 дата публикации

METHODS AND MATERIALS FOR MAINTAINING AND EXPANDING STEM CELL-DERIVED HEPATOCYTE-LIKE CELLS

Номер: US20210009947A1
Автор: Collins Daniel Patrick
Принадлежит:

Culture medium formulations are described that are capable of large-scale expansion of stem cell-derived hepatocyte-like cells while sustaining the activity of those cells to maintain the phenotype and biological characteristics of normal hepatocytes. 1. A composition comprising a culture medium , said medium comprising hydrocortisone , bovine serum albumin , insulin , transferrin , selenium , epithelial growth factor , basic fibroblast growth factor , fibroblast growth factor 4 , hepatocyte growth factor , stem cell factor , oncostatin M , bone morphogenic protein 4 , and interleukin 1 beta.2. The composition of claim 1 , wherein said culture medium is effective for inducing differentiation of human fetal blood multi-lineage progenitor cells (MLPC) or a clonal line of human fetal blood MLPC to cells having a hepatocyte phenotype3. The composition of claim 1 , wherein said culture medium is effective in the long-term growth and maintenance of primate embryonic stem cell-derived hepatocyte-like cells.4. The composition of claim 1 , said culture medium further comprising an antibiotic.5. The composition of claim 1 , said composition further comprising at least one antibody claim 1 , said at least one antibody having binding affinity for alkaline phosphatase claim 1 , alpha fetoprotein claim 1 , albumin claim 1 , c-reactive protein claim 1 , hepatocyte growth factor receptor claim 1 , complement factor VII claim 1 , complement factor IX claim 1 , nestin claim 1 , SOX-17 claim 1 , P450 CYP 1A2 claim 1 , P450 CYP 3A4 claim 1 , asialo-glycoprotein receptor 1 claim 1 , hepatocyte nuclear factor-4 claim 1 , GATA-4 claim 1 , or alpha-1-antitrypsin.6. A method of producing a population of cells having a hepatocyte phenotype claim 1 , said method comprising:a) providing a collagen-coated culturing device housing a purified population of MLPC or a clonal line of MLPC;b) culturing said purified population of MLPC or said clonal line of MLPC with a differentiation medium ...

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Номер записи: 55
14-01-2021 дата публикации

Methods and Materials for Producing Hybrid Cell Lines

Номер: US20210009961A1
Автор: Collins Daniel Patrick, Steer Clifford J.
Принадлежит:

Methods and materials are described for producing immortalized hybrid cells composed of a fusion of immortalized multi-lineage progenitor cells (MLPC) and primary hepatocytes. The hybrid cells express the biological activity of the primary hepatocytes and the immortality and expansion capacities of the immortalized MLPC. The methods of culture and expansion of the resultant hybrid cells and the methods to confirm the characteristics of the hybrid cells are described. 1. A cell population comprising a plurality of hybrid cells , wherein each hybrid cell is composed of an immortalized multi-lineage progenitor cell (MLPC) and a primary somatic cell.2. The cell population of claim 1 , wherein said hybrid cell is created by the fusion of said immortalized MLPC and said primary somatic cell.3. The cell population of claim 1 , wherein said immortalized MLPC comprises a nucleic acid encoding a telomerase reverse transcriptase.4. The cell population of claim 1 , wherein said primary somatic cell is a hepatocyte.5. The cell population of claim 1 , wherein said hybrid cell has the biological activity associated with the primary somatic cell.6. The cell population of claim 1 , wherein the hybrid cell is immortalized and has the expandability of said immortalized MLPC.7. The cell population of claim 1 , wherein the hybrid cells can be expanded continuously in an expansion medium claim 1 , said expansion medium comprising hydrocortisone claim 1 , bovine serum albumin claim 1 , insulin claim 1 , transferrin claim 1 , selenium claim 1 , epithelial growth factor claim 1 , basic fibroblast growth factor claim 1 , fibroblast growth factor 4 claim 1 , hepatocyte growth factor claim 1 , stem cell factor claim 1 , oncostatin M claim 1 , bone morphogenic protein 4 claim 1 , and interleukin 1 beta.8. The cell population of claim 7 , the expansion medium further comprising an antibiotic.9. The cell population of claim 4 , wherein said fusion cells are positive for alkaline phosphatase claim ...

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Номер записи: 56
10-01-2019 дата публикации

Chemical reprogramming to generate neuronal cells

Номер: US20190010451A1
Автор: Mingliang Zhang, Sheng Ding
Принадлежит: J David Gladstone Institutes

Compositions and methods are described herein for chemically inducing cells to change their differentiation state and become neuronal cells.

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Номер записи: 57
10-01-2019 дата публикации

Method for Culturing Limbal Stem Cells by Using Amniotic Membrane Slide Scaffold

Номер: US20190010454A1
Автор: CHUNG So-Hyang, Lee Hyun Jung, SEO Kyung Yul
Принадлежит:

The present invention relates to a method for culturing limbal tissues on an amniotic membrane slide scaffold, thereby enabling the proportion of limbal stem cells in a limbal tissue-derived epithelial cell sheet to be effectively increased, and the same to be cultured. According to the present invention, the proportion of limbal stem cells in in a limbal tissue-derived epithelial cell sheet can be stably and rapidly increased, and thus the success rate can be increased when in limbal tissue-derived epithelial cell sheets are transplanted into a patient with limbal stem cell deficiency. 1. A method for culturing limbal stem cells , comprising:covering a slide glass scaffold with an epithelial cell-removed amniotic membrane for fixation; andculturing limbal tissue on the fixed amniotic membrane.2. The method according to claim 1 , wherein each of the width and length of the amniotic membrane is 28 to 35 mm.3. The method according to claim 1 , wherein epithelial cells of the amniotic membrane are removed using 4 to 6 M urea.4. The method according to claim 1 , wherein each of the width and length of the slide glass is 18 to 28 mm.5. The method according to claim 1 , wherein the limbal tissue is cultured in DMEM/F12(1:1) supplemented with human serum claim 1 , an epithelial cell growth factor (EGF) claim 1 , dimethyl sulfoxide (DMSO) claim 1 , insulin transferrin selenium (ITS) and 0-phosphoethanolamine.6. The method according to claim 5 , wherein the human serum is a human albumin serum claim 5 , and added at 4 to 6% (v/v) of the entire medium.7. The method according to claim 1 , wherein the limbal tissue is cultured for 10 to 14 days.8. The method according to claim 7 , wherein claim 7 , when the limbal tissue is grown to 85 to 95% of the area of the scaffold claim 7 , the limbal tissue is classified as a transplant for a patient. The present invention relates to a method for culturing limbal stem cells using an amniotic membrane slide scaffold. More particularly, ...

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Номер записи: 58
10-01-2019 дата публикации

METHOD TO DIRECT DIFFERENTIATION OF PLURIPOTENT STEM CELLS INTO FUNCTIONAL HEART MUSCLE

Номер: US20190010460A1
Автор: HUDSON James, TIBURCY Malte, Zimmermann Wolfram-Hubertus
Принадлежит: GEORG-AUGUST-UNIVERSITÄT GÖTTINGEN STIFTUNG ÖFFENTLICHEN RECHTS, UNIVERSITÄTSMEDIZIN

The present invention is directed to a method for producing bioengineered heart muscle (BHM) from pluripotent stem cells, generally comprising the steps of inducing mesoderm differentiation, cardiac differentiation, and cardiac maturation by directed tissue formation. The method is a robust, serum-free and reproducible way to produce BHM for multiple applications, and closed herein, as well as to uses of said BHM in pharmacologic and toxicity screenings, and its use in medicine. 115.-. (canceled)16. A bioengineered heart muscle (BHM) produced by a method comprising the steps of(i) cultivating pluripotent stem cells in a basal medium comprising an effective amount of (a) BMP4, Activin A, FGF2, a GSK3-inhibitor, and (b) a serum-free supplement resulting in a final concentration of 0.5-50 mg/ml albumin, 1-100 μg/ml transferrin, 0.1-10 μg/ml ethanol amine, 0.003-0.3 μg/ml sodium selenite, 0.4-40 μg/ml L-Carnitine HCl, 0.1-10 μg/ml Hydrocortisone, 0.05-5 μl/ml Fatty acid supplement, and 0.0001-0.1 μg/ml triodo-L-thyronine (T3), thereby inducing mesoderm differentiation of said pluripotent stem cells;(ii) cultivating the cells obtained in step (i) in a basal medium comprising an effective amount of an inhibitor of the Wnt-signaling pathway and a serum-free supplement as in (i), thereby inducing cardiac differentiation of the cells; and(iii) cultivating the cells obtained in step (ii) in a basal medium comprising an effective amount of a serum-free supplement as in (i), under mechanical stimulation, thereby promoting cardiac maturation.17. The BHM of claim 16 , wherein the BHMa) is capable of being paced at multiple frequencies up to at least 3 Hz; orb) exhibits an increased twitch tension in response to increased resting length and resting tension; or{'sub': '50', 'c) exhibits a calcium EChigher than 0.2 mM; or'}d) exhibits a twitch tension of more than 200 μN; ore) exhibits an inotropic response to 1 μM isoprenaline of more than 40 μN under paced conditions at 0.6 mM ...

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Номер записи: 59
09-01-2020 дата публикации

METHOD FOR PRODUCING MESENCHYMAL STEM CELLS THAT INHIBIT PROLIFERATION OF CANCER CELLS

Номер: US20200010805A1
Автор: KIM Eun-Young, RA Jeong Chan
Принадлежит:

Disclosed are a medium composition for culturing mesenchymal stem cells for the treatment of cancer which can inhibit proliferation of cancer cells, while maintaining differentiation capability and activity thereof, and a method for producing mesenchymal stem cells for the treatment of cancer using the composition. More particularly, disclosed are a medium composition containing vitamin C and aspirin for producing mesenchymal stem cells having improved inhibitory activity against proliferation of cancer cells, and a method for producing mesenchymal stem cells for the treatment of cancer using the composition. 1. A medium composition comprising aspirin for producing mesenchymal stem cells with improved ability to inhibit proliferation of cancer cells.2. The medium composition according to claim 1 , further comprising vitamin C.3. The medium composition according to claim 1 , wherein the medium composition is DMEM or K-SFM containing 5 to 10% FBS and NAC (N-acetyl cysteine).4. The medium composition according to claim 3 , further comprising calcium claim 3 , rEGF claim 3 , insulin and hydrocortisone.5. The medium composition according to claim 1 , wherein the mesenchymal stem cells are derived from tissues selected from the group consisting of adipose claim 1 , uterus claim 1 , bone marrow claim 1 , muscles claim 1 , placenta claim 1 , umbilical cord blood claim 1 , urine and skin.6. The medium composition according to claim 1 , wherein a concentration of the aspirin is 0.1 mM to 1 mM.7. The medium composition according to claim 1 , wherein the cancer cells are breast cancer claim 1 , pancreatic cancer claim 1 , glioma claim 1 , gliosarcoma claim 1 , anaplastic astrocytoma claim 1 , medulloblastoma claim 1 , lung cancer claim 1 , small cell lung cancer claim 1 , cervical carcinoma claim 1 , colon cancer claim 1 , rectal cancer claim 1 , chordoma claim 1 , throat cancer claim 1 , Kaposi's sarcoma claim 1 , lymphatic sarcoma claim 1 , lymphatic endothelial sarcoma claim ...

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Номер записи: 60
19-01-2017 дата публикации

INDUCING BROWN FAT FATE AND FUNCTION

Номер: US20170014455A1
Автор: Ding Sheng, Nie Baoming
Принадлежит:

Methods and compositions are described herein for generating brown adipose cells and tissues that involve contacting one or more starting cells with bexarotene, ciclopirox, IOX2, or combinations thereof. When administered in vivo, subjects receiving bexarotene, ciclopirox, IOX2, or combinations thereof have reduced white adipose tissue mass (with enhanced beige features) as well as enlarged brown fat tissue compared to a control mammal that did not receive the bexarotene, ciclopirox, IOX2, or combinations thereof. The subjects also have increased energy expenditure, generate more heat, and/or consume more oxygen, than a control mammal that did not receive the bexarotene, ciclopirox, IOX2, or combinations thereof. 1. A method of generating brown adipose cells from non-brown adipose starting cells , comprising contacting the starting cells with bexarotene , ciclopirox , IOX2 , or combinations thereof , to thereby generate brown adipose cells.2. The method of claim 1 , wherein the starting cells are selected from the group of myoblasts claim 1 , adipocytes claim 1 , pre-adipocytes claim 1 , mesenchymal precursor cells claim 1 , multipotent stem cells claim 1 , pluripotent stem cells claim 1 , unipotent stem cells claim 1 , fibroblasts claim 1 , white adipocytes claim 1 , and any combination thereof.3. The method of claim 1 , which inhibits white adipocyte cell generation.4. The method of claim 1 , further comprising contacting the one or more starting cells with retinoic acid claim 1 , 9-cis retinoic acid claim 1 , all-trans 3 claim 1 ,4-didehydro retinoic acid claim 1 , 4-oxo retinoic acid claim 1 , retinol claim 1 , rosigliotazone claim 1 , forskolin claim 1 , or any combination thereof.6. The method of claim 1 , performed in vitro.7. The method of claim 6 , further comprising administering the one or more brown adipose cells to a mammal.8. The method of claim 1 , performed in vivo.9. The method of claim 8 , wherein the bexarotene claim 8 , ciclopirox claim 8 , IOX2 ...

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Номер записи: 61
18-01-2018 дата публикации

GENERATION OF UNIFORM HEPATOCYTES FROM HUMAN EMBRYONIC STEM CELLS BY INHIBITING TGF-BETA and METHODS OF MAINTAINING HEPATIC CULTURES

Номер: US20180015126A1
Автор: James A. Thomson, Srikumar Sengupta
Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

This disclosure relates generally to new methods of maintaining the expression of hepatic genes in human hepatocytes and method for maintaining the functional hepatic enzyme activity of primary hepatocytes in culture. The disclosure also encompasses new methods of deriving a population of pure hepatocytes without selecting or sorting the cells from the cultured pluripotent cells.

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Номер записи: 62
17-01-2019 дата публикации

METHODS OF TREATING ISCHEMIA

Номер: US20190015454A1
Автор: Mendlein John D., Multani Pratik S., Robbins David, Shoemaker Dan
Принадлежит:

The invention provides compositions comprising stem and/or progenitor cells that have been treated to enhance the therapeutic properties of the cells for treating ischemia. In particular, the present invention relates to the use of stem and/or progenitor cells having enhanced therapeutic properties to treat an ischemic tissue, a tissue damaged by ischemia, or at least one symptom associated with an ischemic tissue or a tissue damaged by ischemia. 1. A method of increasing stem or progenitor cell homing to an ischemic tissue or a tissue damaged by ischemia , comprising:(a) treating stem or progenitor cells ex vivo with a prostaglandin pathway agonist and optionally, a glucocorticoid, under conditions sufficient to increase CXCR4 gene expression at least two fold in the treated stem or progenitor cells compared to non-treated stem or progenitor cells; and(b) administering a composition, comprising the treated stem or progenitor cells, to a subject having an ischemic tissue or a tissue damaged by ischemia.2. A method of treating a subject having an ischemic tissue or a tissue damaged by ischemia comprising: administering a therapeutically effective amount of a composition comprising stem or progenitor cells treated ex vivo with a prostaglandin pathway agonist and optionally , a glucocorticoid , under conditions sufficient to increase CXCR4 gene expression at least two fold in the treated stem or progenitor cells compared to non-treated stem or progenitor cells.3. A method of ameliorating at least one symptom associated with an ischemic tissue or a tissue damaged by ischemia in a subject comprising: administering a therapeutically effective amount of a composition comprising stem or progenitor cells treated ex vivo with a prostaglandin pathway agonist and optionally , a glucocorticoid , under conditions sufficient to increase CXCR4 gene expression at least two fold in the treated tem or progenitor cells compared to non-treated stem or progenitor cells.4. A method of ...

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Номер записи: 63
21-01-2016 дата публикации

CELL CULTURE MEDIA COMPOSITION AND METHODS OF PRODUCING THEREOF

Номер: US20160017277A1
Автор: Sunstrom Noelle
Принадлежит:

A serum free cell culture media, wherein the media is adapted to be conditioned by culturing a first set of eukaryotic cells in the media, wherein the first set of eukaryotic cells use an expression vector to excrete levels of desired complex proteins into the media; wherein said desired complex proteins include human Growth Hormone (hGH), Growth Hormone-like growth factors, insulin-like growth factors, insulin, modified insulins, cytokines, mitogenic proteases and mixtures thereof; and wherein the media is adapted to grow a set of eukaryotic cells.

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Номер записи: 64
21-01-2016 дата публикации

METHODS OF INCREASING INSULIN CONTENT IN CELLS

Номер: US20160017290A1
Автор: Efrat Shimon, Sintov Elad
Принадлежит:

A method of ex-vivo increasing insulin content in progenitor cells which express Zinc Finger E-Box Binding Homeobox 1 (ZEB-1) is disclosed. The method comprises contacting the progenitor cells with an inhibitory agent directed against a polypeptide, wherein the RNA transcript encoding said polypeptide is targeted by miRNA-200c, said polypeptide being selected from the group consisting of ZEB-1, SOX-2 and SOX-6.

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Номер записи: 65
18-01-2018 дата публикации

METHOD FOR DIFFERENTIATION INTO RETINAL GANGLION CELLS FROM STEM CELLS

Номер: US20180016552A1
Автор: KIM Ji Yeon, PARK Sung Sup
Принадлежит:

Provided are a method of preparing retinal ganglion cells by differentiation of stem into retinal ganglion cells, retinal ganglion cells differentiated by the method, a method of screening for a death inhibitor or a proliferation promoter of retinal ganglion cells using the retinal ganglion cells differentiated by the method, a kit of screening for the death inhibitor or the proliferation promoter of retinal ganglion cells including the retinal ganglion cells differentiated by the method, a pharmaceutical composition for treating glaucoma or optic neuropathy including the retinal ganglion cells, a method of treating glaucoma or optic neuropathy including the step of administering the retinal ganglion cells to a subject suspected of having glaucoma or optic neuropathy, and a method of preparing a mature retinal ganglion cell line. 1. A method of preparing mature retinal ganglion cells by differentiation of stem cells into mature retinal ganglion cells , comprising:(a) culturing retinal progenitor cells in a medium comprising an IGF1R (insulin-like growth factor-1 receptor) activator and a Wnt signaling pathway activator to differentiate them into immature retinal ganglion cells; and(b) culturing the immature retinal ganglion cells in a medium whose composition does not comprise the Wnt signaling pathway activator from that of the medium of step (a).2. The method of claim 1 , wherein the medium of step (a) comprises an IGF1R activator claim 1 , a BMP (bone morphogenetic protein) signaling pathway inhibitor claim 1 , an FGF (fibroblast growth factor) signaling pathway activator claim 1 , and a Wnt signaling pathway activator.3. The method of claim 2 , wherein step (b) comprises culturing the immature retinal ganglion cells in a medium whose composition does not comprise the BMP signaling pathway inhibitor claim 2 , FGF signaling pathway activator claim 2 , and Wnt signaling pathway activator claim 2 , and comprises an Shh (sonic hedgehog) signaling pathway activator ...

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Номер записи: 66
18-01-2018 дата публикации

METHOD OF INDUCING BETA CELLS FROM URINE-DERIVED CELLS USING SMALL MOLECULES

Номер: US20180016556A1
Автор: HAN Yanchuang, Kim Jihee, Kim Wookyung, Yang Junyong, ZHOU Xin-Fu
Принадлежит:

The disclosure relates to a method of producing induced beta cells from urine-derived cells, the method comprising providing urine-derived cells; inducing the urine-derived cells by culturing said urine-derived cells in a primary induction culture medium comprising an effective amount of at least one small molecule reprogramming factor(s) for a first period of time to obtain induced endoderm cells; inducing the induced endoderm cells by culturing said induced endoderm cells in a secondary induction culture medium comprising an effective amount of at least one small molecule reprogramming factor(s) for a second period of time to obtain induced pancreatic precursor cells; and inducing the induced pancreatic precursor cells by culturing said pancreatic precursor cells in a tertiary induction culture medium comprising an effective amount of at least one small molecule reprogramming factor(s) for a third period of time to obtain induced beta cells. 1. A method of producing induced beta cells from urine-derived cells , the method comprising:(a) providing urine-derived cells;(b) inducing the urine-derived cells provided in step (a) by culturing said urine-derived cells in a primary induction culture medium comprising an effective amount of at least one small molecule reprogramming factor(s) for a first period of time to obtain induced endoderm cells;(c) inducing the induced endoderm cells obtained in step (b) by culturing said induced endoderm cells in a secondary induction culture medium comprising an effective amount of at least one small molecule reprogramming factor(s) for a second period of time to obtain induced pancreatic precursor cells; and(d) inducing the induced pancreatic precursor cells obtained in step (c) by culturing said pancreatic precursor cells in a tertiary induction culture medium comprising an effective amount of at least one small molecule reprogramming factor(s) for a third period of time to obtain induced beta cells.2. The method of claim 1 , ...

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Номер записи: 67
16-01-2020 дата публикации

Molecular Composition for Enhancing and Rejuvenating Maintenance and Repair of Mammalian Tissues

Номер: US20200016233A1
Автор: Conboy Irina M., Conboy Michael J., COUSIN Wendy, ELABD Christian, Schaffer David V., Yousef Hanadie
Принадлежит:

Methods, pharmaceutical compositions, and kits are provided for treating a subject with an effective amount of an oxytocin receptor (OXTR) agonist and an effective amount of an ALK5 antagonist. In certain aspects, the OXTR agonist may be oxytocin or an oxytocin analog (e.g., a small molecule). The ALK 5 antagonist may be a small molecule, such as 2-(3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine, LY2157299, A 83-01, D 4476, GW 788388, LY 364947, RepSox, SB 431542, SB 505124, SB 525334, or SD 208. In certain aspects, the amounts of the OXTR agonist and ALK5 antagonist may be sufficient to induce muscle regeneration and/or neural cell regeneration in the subject. 137. -. (canceled)38. A composition comprising:an OXTR agonist;an ALK5 antagonist; anda pharmaceutically acceptable excipient.39. The composition of claim 38 , wherein the amount of the OXTR agonist is in the range of 7.5 nM-30 nM.40. The composition of claim 38 , wherein the amount of the ALK5 antagonist is in the range of 0.05 μM-3 μM.41. The composition of claim 38 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:50.42. The composition of claim 38 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 50:1.43. The composition of claim 38 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:40.44. The composition of claim 38 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:30.45. The composition of claim 38 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 40:1.46. The composition of claim 38 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:25.47. The composition of claim 38 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 25:1.48. The composition of claim 38 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:10.49. The composition of claim 38 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 10:1.50. The composition of claim 38 , wherein the ratio ...

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Номер записи: 68
17-01-2019 дата публикации

SUPPORTED IN VITRO DEVELOPED TISSUE CULTURE AND CULTURING METHODS

Номер: US20190017016A1
Автор: KNOBLICH Jürgen, Lancaster Madeline A.
Принадлежит:

An elongated or fiber-supported multicellular aggregation of multipotent cells, wherein multipotent cells are arranged in an oblong or longish arrangement with an aspect ratio of a prolate dimension to a perpendicular dimension of at least 2:1, or supported by a fibrous structure, and wherein the aggregate contains cells at different stages of differentiation, and the aggregate contains polar cells; methods of generating such aggregates; methods of developing the aggregates further into tissue organoids and kits for such methods. 115-. (canceled)16. A method of generating an elongated or fiber-supported multicellular aggregation of neural lineage with neuronal differentiated cells comprising the steps of:a) providing a plurality of pluripotent or non-human totipotent cells (i) that are located in an oblong or longish arrangement adhered to a support, said support has a length of 20 μm to 20 mm and a diameter of 1 μm to 60 μm, wherein said support is a biocompatible polymer that is not a biopolymer or wherein said support is a protein, or (ii) that are arranged on a fibrous structured support, and said support has a length of 20 μm to 20 mm and a diameter of 1 μm to 60 μm, wherein said fibrous structured support is a biocompatible polymer that is not a biopolymer or wherein said fibrous structured support is a protein; andb) letting said cells grow and differentiate in said arrangement, wherein said cells form intercellular bonds and adhere to each other;wherein said cells are stimulated to differentiate by a contacting the cells with a neuronal growth or differentiation factor.17. The method of claim 16 , wherein the arrangement has an aspect ratio of a prolate dimension to a perpendicular dimension of at least 2:1.18. The method of claim 16 , wherein said support is non-porous or has a porosity of less than 5% (v/v) of the supports volume.19. The method of claim 16 , wherein said support is a polymer microfilament and/or is biocompatible but not bioactive.20. The ...

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Номер записи: 69
17-01-2019 дата публикации

Generation of Expandable Cardiovascular Progenitor Cells

Номер: US20190017029A1
Автор: Cao Nan, Ding Sheng, Zhang Yu
Принадлежит:

Methods and compositions for expanding cardiovascular progenitor cells are described herein that include use of compositions and culture media that have at least the following components: BMP4, Activin A, a glycogen synthase kinase 3 inhibitor, and an inhibitor of FGF, VEGF, and PDGF signaling. The methods include contacting cardiovascular progenitor cells with a culture medium having BMP4, Activin A, a glycogen synthase kinase 3 inhibitor, and an inhibitor of FGF, VEGF, and PDGF signaling, to generate an expanded cardiovascular progenitor cell population. 1. A method for expanding cardiovascular progenitor cells comprising contacting the cardiovascular progenitor cells with a culture medium comprising BMP4 , Activin A , a glycogen synthase kinase 3 inhibitor , and an inhibitor of FGF , VEGF , and PDGF signaling , to generate an expanded cardiovascular progenitor cell population.2. The method of claim 1 , wherein the glycogen synthase kinase 3 inhibitor is CHIR99021 claim 1 , 1-azakenpaullone claim 1 , AR-A014418 claim 1 , indirubin-3′-monoxime claim 1 , 5-Iodo-indirubin-3′-monoxime claim 1 , kenpaullone claim 1 , SB-415286 claim 1 , SB-216763 claim 1 , 2-anilino-5-phenyl-1 claim 1 ,3 claim 1 ,4-oxadiazole) claim 1 , (Z)-5-(2 claim 1 ,3-Memylenedioxyphenyl)imidazolidine-2 claim 1 ,4-dione claim 1 , TWS119 claim 1 , CHIR98014 claim 1 , SB415286 claim 1 , Tideglusib claim 1 , LY2090314 claim 1 , a lithium salt claim 1 , or a combination thereof.3. The method of claim 1 , wherein the inhibitor of FGF claim 1 , VEGF claim 1 , and PDGF signaling is SU5402 claim 1 , AP 24534 claim 1 , FIIN 1 hydrochloride claim 1 , R 1530 claim 1 , SU 6668 claim 1 , Sunitinib malate claim 1 , Toceranib; Brivanib alaninate claim 1 , or a combination thereof.4. The method of claim 1 , wherein the BMP4 is present in the culture medium at a concentration of 0.5 to 50 ng/mL claim 1 , about 0.5 to 20 ng/ml.5. The method of claim 1 , wherein the Activin A is present in the culture medium at a ...

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Номер записи: 70
17-01-2019 дата публикации

SC-BETA CELLS AND COMPOSITIONS AND METHODS FOR GENERATING THE SAME

Номер: US20190017031A1
Автор: Gürtler Mads, Melton Douglas A., Millman Jeffrey R., Pagliuca Felicia J., PETERSON Quinn P., Segel Michael Saris
Принадлежит:

Disclosed herein are methods, compositions, kits, and agents useful for inducing β cell maturation, and isolated populations of SC-β cells for use in various applications, such as cell therapy. 1. A composition comprising a non-native pancreatic β cell , wherein:(a) the non-native pancreatic β cell comprises one or more crystalline insulin granules;(b) the non-native pancreatic β cell expresses the following genes: INS, PDX1, NKX6-1, and ZNT8; and(c) the non-native pancreatic β cell exhibits an in vitro glucose-stimulated insulin secretion response to a first glucose challenge and a second glucose challenge when the first glucose challenge and the second glucose challenge are applied sequentially.2. The composition of claim 1 , wherein the non-native pancreatic β cell exhibits an in vitro glucose-stimulated insulin secretion response to a first glucose challenge claim 1 , a second glucose challenge claim 1 , and a third glucose challenge claim 1 , when the first glucose challenge claim 1 , the second glucose challenge and the third glucose challenge are applied sequentially.3. The composition of claim 1 , wherein the non-native pancreatic β cell is generated from a stem cell.4. The composition of claim 3 , wherein the stem cell is a human stem cell.5. The composition of claim 3 , wherein the stem cell is an embryonic stem cell.6. The composition of claim 3 , wherein the stem cell is an induced pluripotent stem cell.7. The composition of claim 1 , wherein the non-native pancreatic β cell exhibits a glucose-stimulated calcium flux in vitro.8. The composition of claim 1 , wherein the non-native pancreatic β cell further expresses at least one gene selected from the group consisting of MAFA claim 1 , PAX6 claim 1 , NEUROD1 claim 1 , GCK claim 1 , SLC2A1 claim 1 , PCSK1 claim 1 , KCNJ11 claim 1 , ABCC8 claim 1 , SNAP25 claim 1 , RAB3A claim 1 , GAD2 claim 1 , PTPRN claim 1 , NKX2-2 claim 1 , and PAX4.9. The composition of claim 1 , wherein the non-native pancreatic β ...

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Номер записи: 71
21-01-2021 дата публикации

ISLET CELL MANUFACTURING COMPOSITIONS AND METHODS OF USE

Номер: US20210017157A1
Автор: Pagliuca Felicia J., Thiel Austin, Thompson Evrett, Yasin Jihad
Принадлежит:

Disclosed herein are compositions and methods useful for manufacturing SC-β cell, and isolated populations of SC-β cells for use in various applications, such as cell therapy. 1103-. (canceled)105. The method of claim 104 , wherein the composition further comprises a growth factor from the transformation growth factor β (TGF-β) superfamily.106. The method of claim 105 , further comprising differentiating the population of primitive gut tube cells to generate a cell cluster comprising non-native pancreatic β cells capable of having a glucose stimulated insulin secretion (GSIS) response.107. The method of claim 106 , wherein the differentiating of the population of primitive gut tube cells generates a cell cluster that comprises a higher percentage of non-native pancreatic β cells capable of having a GSIS response as compared to a cell cluster differentiated from a comparable population of primitive gut tube cells without the contacting with the composition comprising the BMP signaling pathway inhibitor and the growth factor from the transformation growth factor β (TGF-β) superfamily.108. The method of claim 106 , wherein the differentiating of the population of primitive gut tube cells generates a cell cluster that comprises non-native pancreatic β cells that has a higher glucose-stimulated insulin secretion (GSIS) stimulation index than a cell cluster comprising non-native pancreatic β cells differentiated from a comparable population of primitive gut tube cells without the BMP signaling pathway inhibitor or the growth factor from the transformation growth factor β (TGF-β) superfamily.109. The method of claim 108 , wherein the GSIS stimulation index is calculated as a ratio of insulin secretion in response to a first glucose concentration to insulin secretion in response to a second glucose concentration claim 108 , and wherein said first glucose concentration is about 10 to about 50 mM claim 108 , and said second glucose concentration is about 1 mM to 5 mM.110. The ...

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Номер записи: 72
21-01-2021 дата публикации

Pac1 antibodies and uses thereof

Номер: US20210017261A1
Автор: Agnes Eva Hamburger, Bryna FUCHSLOCHER, Cen Xu, Christopher MOHR, Derek E. Piper, Irwin Chen, Kenneth William Walker, Kevin Graham, Mark Leo Michaels, Neeraj Jagdish Agrawal, Su Chong, Zhulun Wang
Принадлежит: AMGEN INC

The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.

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Номер записи: 73
21-01-2021 дата публикации

PROCESS FOR PRODUCING CARDIAC ORGANOIDS

Номер: US20210017496A1
Автор: DRAKHLIS Lika, Zweigerdt Robert
Принадлежит:

The invention provides an in vitro process for producing a cardiac organoid from cultivated pluripotent stem cells, which cardiac organoids reproducibly have a structure of specific cardiac cell layers. 1. Process for in vitro producing a cardiac organoid comprisinga) providing cultivated pluripotent stem cells (PSC) in a suspension in a first culture medium,b) centrifuging the PSC in a first vessel having a U-shaped bottom to localize the PSC at the bottom of the first vessel,c) incubating the PSC localized at the bottom of the first vessel under the first medium under cell culture conditions,d) optionally removing the first medium from the PSC localized at the bottom of the first vessel,e) embedding the PSC within hydro gel,f) incubating the PSC embedded within the hydrogel for solidifying the hydrogel,g) covering the cells embedded in the solidified hydrogel with a second cell culture medium and incubating under cell culture conditions,h) removing the second medium from the cells and adding a third cell culture medium containing a first differentiation factor having activity to induce the WNT pathway and incubating under cell culture conditions for at least 6 h,i) removing the third medium from the cells and adding a fourth cell culture medium not containing a differentiation factor or containing an agent neutralizing the activity of the first differentiation factor, and incubating under cell culture conditions for at least 6 h,j) removing the medium from the cells and adding a fifth cell culture medium containing a second differentiation factor having activity to inhibit the WNT pathway and incubating under cell culture conditions for at least 1 d,k) removing the fifth medium from the cells and adding a sixth medium not containing insulin and not containing a differentiation factor having activity to induce or to inhibit the WNT pathway, and incubating under cell culture conditions for at least 1 d,l) removing the sixth medium from the cells and adding a seventh ...

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Номер записи: 74
16-01-2020 дата публикации

ANTERIOR ENDODERM CELLS AND METHODS OF PRODUCTION

Номер: US20200017824A1
Автор: "DAmour Kevin Allen", Agulnick Alan D., Baetge Emmanuel E., Eliazer Susan
Принадлежит: VIACYTE, INC.

Disclosed herein are cell cultures comprising PDX1-positive endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified PDX1-positive endoderm cells as well as methods for enriching, isolating and purifying PDX1-positive endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of endoderm cells, such as PDX1-positive foregut endoderm cells and PDX1-negative definitive endoderm cells, are also disclosed. 1. An in vitro cell culture method for producing human anterior foregut endoderm cells , comprising , contacting a population of human pluripotent stem cells with an effective amount of a retinoid to produce human anterior foregut endoderm cells.2. The in vitro cell culture method of claim 1 , wherein the RA is provided to the population of human pluripotent stem cells at a concentration of about 1 μM.3. The in vitro cell culture method of claim 1 , wherein the human anterior foregut endoderm cells express HOXA3.4. An in vitro cell culture method for producing human midgut endoderm cells claim 1 , comprising claim 1 , contacting a population of human pluripotent stem cells with an effective amount of a retinoid to produce human midgut endoderm cells.5. The in vitro cell culture method of claim 4 , wherein the retinoid is retinoic acid (RA).6. The in vitro cell culture method of claim 5 , wherein the RA is provided to the population of human pluripotent stem cells at a concentration of about 0.2 μM.7. The in vitro cell culture method of claim 4 , wherein the human midgut endoderm cells express HOXC6.8. An in vitro cell culture method for producing human hindgut endoderm cells claim 4 , comprising claim 4 , contacting a population of human pluripotent stem cells with an effective amount of a retinoid to produce human hindgut endoderm cells.9. The in vitro cell culture method of claim 8 , wherein the retinoid is retinoic acid (RA).10. ...

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Номер записи: 75
16-01-2020 дата публикации

MonoMac-1 Cells Expressing CD16 and CD163

Номер: US20200018745A1
Автор: Rappaport Jay, Vakili Sarah
Принадлежит:

The invention provides monocytes expressing CD16 and CD163 and experimental system for drug screening or evaluating drug candidates where the modulation of CD16 and CD163 is desired. 1. A monocyte , wherein the monocyte expresses at least one protein selected from the group consisting of CD16 , CD163 , CD4 and a combination thereof.2. The monocyte of claim 1 , wherein the monocyte is cultured in the presence of at least one of phorbol-12-myristate-13-acetate (PMA) claim 1 , lipopolysaccharide (LPS) claim 1 , macrophage colony-stimulating factor (MCSF) claim 1 , dexamethasone (DEX) claim 1 , TNFα and IFNγ.3. The monocyte of claim 1 , wherein the monocyte is a MonoMac-1 cell.4. A method of culturing monocyte cells to induce the expression of a protein selected from the group consisting of CD16 claim 1 , CD163 claim 1 , CD4 and a combination thereof.5. The method of claim 4 , comprising culturing a monocyte cell in the presence of one or more of PMA claim 4 , LPS claim 4 , MCSF claim 4 , DEX claim 4 , TNFα and IFNγ.6. The method of claim 4 , comprising culturing a monocyte cell line in the presence of one or more of PMA and LPS.7. The method of claim 6 , wherein the monocyte cells are cultured for at least three days.8. The method of claim 6 , further comprising culturing the monocyte cell line in the presence of at least one of MCSF claim 6 , DEX claim 6 , TNFα and IFNγ.9. The method of claim 4 , comprising culturing the monocytes in the presence of one or more of PMA and LPS followed by culturing the monocytes in the presence of at least one of MCSF claim 4 , DEX claim 4 , TNFα and IFNγ.10. The method of claim 9 , wherein the monocyte cells are cultured for at least three days in the presence of PMA and LPS prior to the addition of MCSF claim 9 , DEX claim 9 , TNFα and IFNγ.11. A method of screening for a compound that modulates the level or activity of at least one protein selected from the group consisting of CD16 claim 9 , CD163 claim 9 , CD4 and a combination ...

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Номер записи: 76
28-01-2016 дата публикации

Methods for production of platelets from pluripotent stem cells and compositions thereof

Номер: US20160022736A1
Автор: Qiang FENG, Robert P. Lanza, Shi-Jiang Lu
Принадлежит: Advanced Cell Technology Inc

Methods for production of platelets from pluripotent stem cells, such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are provided. These methods may be performed without forming embryoid bodies or clusters of pluripotent stem cells, and may be performed without the use of stromal inducer cells. Additionally, the yield and/or purity can be greater than has been reported for prior methods of producing platelets from pluripotent stem cells. Also provided are compositions and pharmaceutical preparations comprising platelets, preferably produced from pluripotent stem cells.

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Номер записи: 77
25-01-2018 дата публикации

METHODS FOR ENGINEERING ALLOGENEIC AND IMMUNOSUPPRESSIVE RESISTANT T CELL FOR IMMUNOTHERAPY

Номер: US20180021379A1
Автор: Galetto Roman, Gouble Agnès, GROSSE STÉPHANIE, MANNIOUI CÉCILE, POIROT Laurent, Scharenberg Andrew, Smith Julianne
Принадлежит: CELLECTIS

Methods for developing engineered T-cells for immunotherapy that are both non-alloreactive and resistant to immunosuppressive drugs. The present invention relates to methods for modifying T-cells by inactivating both genes encoding target for an immunosuppressive agent and T-cell receptor, in particular genes encoding CD52 and TCR. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections. 125-. (canceled)26. A method for treating a cancer patient using immunotherapy comprising:providing primary human T cells from a single donor;co-electroporating into said primary human T-cells:(a) RNAs encoding two half TALE-nucleases that cleave a first gene, and(b) RNAs encoding two half TALE-nucleases that cleave a second gene,to generate a population of transfected human T cells comprising at least 15.5% doubly-inactivated human T-cells having both first and second genes inactivated;modifying the population of doubly inactivated human T-cells to express a chimeric antigen receptor; andinfusing the population of doubly inactivated human T-cells into said cancer patient for immunotherapy treatment.27. The method of claim 26 , wherein the first gene is CD52 or glucocorticoid receptor (GR).28. The method of claim 26 , wherein the second gene encodes T-cell receptor alpha.29. The method of claim 27 , wherein the second gene encodes T-cell receptor alpha.30. A method for treating a cancer patient using immunotherapy comprising:providing primary human T cells from a single donor;modifying the primary human T cells to express a chimeric antigen receptor;co-electroporating into said modified primary human T-cells:(a) RNAs ...

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Номер записи: 78
28-01-2016 дата публикации

Somatic cell nuclear transfer methods

Номер: US20160024528A1
Автор: Dietrich M. Egli
Принадлежит: Dietrich M. Egli

The present invention provides methods for making reconstructed diploid human oocytes comprising the diploid genome of a human somatic cell, and also methods for making human nuclear transfer embryos, human embryonic stem cells, and human differentiated cells therefrom. The present invention also provides reconstructed human oocytes, human nuclear transfer embryos, human embryonic stem cells, and differentiated cells made using such methods, as well as compositions and kits useful in performing such methods.

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Номер записи: 79
22-01-2015 дата публикации

INCREASED AQUAPORIN EXPRESSION ON CELLULAR MEMBRANE TO IMPROVE CRYOPRESERVATION EFFICIENCY

Номер: US20150024406A1
Автор: Coger-Simmons Robin N., Kumar Balasubramanian Karthik, Lee Charles, Schrum Laura Whritenour
Принадлежит:

A method of storing mammalian cells or tissue (e.g., liver cells or hepatocytes) for subsequent use comprises the steps of: (a) contacting the cells or tissue in vitro to a choleretic agent in an effective amount; (b) combining said cells or tissue with a cryopreservative; (c) freezing said cells or tissue, and then (d) storing said frozen cells or tissue in frozen form for subsequent use. 1. A method of storing mammalian cells or tissue for subsequent use , comprising the steps of:(a) contacting the cells or tissue in vitro to a choleretic agent in an effective amount;(b) combining said cells or tissue with a cryopreservative; and then(c) freezing said cells or tissue.2. The method of claim 1 , further comprising the step of:(d) storing said frozen cells or tissue in frozen form for subsequent use.3. The method of claim 1 , wherein said cells or tissue are liver cells or tissue.4. The method of claim 1 , wherein said cells or tissue comprise hepatocytes.5. The method of claim 1 , wherein said choleretic agent comprises DiButyryl cAMP (BtcAMP) or glucagon.6. The method of claim 1 , wherein said cryopreservative comprises glycerol.7. The method of claim 1 , wherein said mammalian cells or tissue are human cells or tissue.8. The method of claim 1 , wherein said choleretic agent is contacted to said cells or tissue in an amount effective to increase the expression of aquaporins on cell membranes thereof.9. The method of claim 8 , wherein said aquaporins comprise Aquaporin-8 (AQP8).10. The method of claim 2 , wherein said storing step is carried out for at least one week.11. Frozen mammalian cells or tissues produced by the process of and stored in sterile form in a container.12. A method of providing live mammalian cells or tissue claim 1 , comprising the step of:{'claim-ref': {'@idref': 'CLM-00011', 'claim 11'}, '(a) thawing cells or tissue of .'}13. The method of claim 12 , further comprising the step of:(b) rinsing said cells or tissue with an aqueous solution to ...

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Номер записи: 80
26-01-2017 дата публикации

PDX1-EXPRESSING DORSAL AND VENTRAL FOREGUT ENDODERM

Номер: US20170022474A1
Автор: "DAmour Kevin Allen", Agulnick Alan D., Baetge Emmanuel E., Eliazer Susan
Принадлежит: VIACYTE, INC.

Disclosed herein are cell cultures comprising dorsal and/or ventral PDX1-positive foregut endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified dorsal and/or ventral PDX1-positive foregut endoderm cells as well as methods for enriching, isolating and purifying dorsal and/or ventral PDX1-positive foregut endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of dorsal and/or ventral PDX1-positive foregut endoderm cells, are also disclosed. 1. A method of producing human foregut endoderm cells , the method comprising:culturing definitive endoderm cells in a medium wherein the medium is eithera) substantially free of TGFβ superfamily growth factor; orb) comprises a FGF-family growth factorthereby producing human foregut endoderm cells.2. A method of producing human foregut endoderm cells , the method comprising: culturing definitive endoderm cells in a medium substantially free of a TGFβ superfamily growth factor thereby producing human foregut endoderm cells.3. A method of producing human foregut endoderm cells , the method comprising: culturing definitive endoderm cells in a medium comprising a FGF-family growth factor thereby producing human foregut endoderm cells.4. The method of claim 1 , wherein the definitive endoderm cells are cultured in a medium substantially free of TGFβ superfamily growth factor and comprising a FGF-family growth factor.5. The method of claim 1 , wherein the foregut endoderm cells express a marker selected from the group consisting of SOX17 claim 1 , HNF1β and FOXA1 and do not substantially express pancreatic-duodenal homeobox factor-1 (PDX1).6. The method of claim 1 , wherein at least 10% of the human cells are foregut endoderm cells that express a marker selected from the group consisting of SOX17 claim 1 , HNF1β and FOXA1 claim 1 , and do not substantially express PDX1.7. The method of claim 1 , ...

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Номер записи: 81
24-01-2019 дата публикации

Treatment of Glioma by Amniotic Fluid Stem Cells and Exosomes Derived Thereof

Номер: US20190022147A1
Автор: Ichim Thomas, Kesari Santosh, Patel Amit
Принадлежит: Creative Medical Technologies, Inc

Disclosed are compositions of matter, therapeutic protocols, and cellular reprogramming means to inhibit glioma or other brain neoplasia. In one embodiment the invention provides administration of amniotic fluid derived stem cells at concentrations of 1 million to 200 million administered in a manner to provide a differentiation stimulation, resulting in reduction of malignant potential. In other embodiments, an unexpected synergy of cancer inhibitory soluble factor production is disclosed by combined cultures between amniotic fluid stem cells and monocytes. In all embodiments cells may be autologous or allogeneic. The invention provides means of augmenting efficacy of immunotherapy, chemotherapy, and radiotherapy. 1. A method of treating glioma comprising the steps of: a) identifying a patient suffering from glioma; b) obtaining amniotic fluid; c) extracting from said amniotic fluid a population of cells with ability in inhibit neoplastic activity of glioma or other brain neoplasms; d) expanding said amniotic fluid cells with ability in inhibit neoplastic activity of glioma or other brain neoplasms in a manner to allow for increased number of cells while maintaining said ability inhibit neoplastic activity of glioma or other brain neoplasms , optionally treating said cells under conditions resembling the tumor microenvironment; and e) administering said expanded amniotic fluid derived cells into a patient suffering from glioma.2. The method of claim 1 , wherein said amniotic fluid stem cells are treated under conditions of hypoxia.3. The method of claim 1 , wherein said glioma refers to: a) a glioblastoma; b) a glioblastoma multiforme; c) an oligodendroglioma; d) a primitive neuroectodermal tumor; e) an astrocytoma; f) an ependymoma; g) an oligodendroglioma; h) a medulloblastoma; i) a meningioma; j) a pituitary carcinoma; k) a neuroblastoma; or 1) a craniopharyngioma.4. The method of claim 2 , wherein said conditions resembling tumor microenvironment are achieved ...

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Номер записи: 82
25-01-2018 дата публикации

MODALITIES FOR THE TREATMENT OF DEGENERATIVE DISEASES OF THE RETINA

Номер: US20180023052A1
Автор: KLIMANSKAYA Irina V., Lanza Robert P.
Принадлежит: Astellas Institute for Regenerative Medicine

This invention relates to methods for improved cell-based therapies for retinal degeneration and for differentiating human embryonic stem cells and human embryo-derived into retinal pigment epithelium (RPE) cells and other retinal progenitor cells. 1. A method of treating or preventing retinal degeneration , comprising use of a cell selected from the group consisting of at least one of: RPE cells , RPE-like cells , RPE or RPE-like progenitors derived from mammalian embryonic stem cells.2. The method of claim 1 , wherein the condition of retinal degeneration is selected from the group consisting of at least one of: retinitis pigmentosa and macular degeneration.3. The method of claim 1 , further comprising transplantation of the cell by vitrectomy surgery into the subretinal space of the eye.4. The method of claim 3 , wherein the cells are transplanted in a suspension claim 3 , matrix claim 3 , or substrate.5. The method of claim 2 , wherein the retinitis pigmentosa is associated with an animal model.6. The method of claim 5 , where in the animal model is selected from the group consisting of: rd mouse claim 5 , RPE-65 knockout mouse claim 5 , tubby-like mouse claim 5 , RCS rat claim 5 , Abyssinian cat claim 5 , cone degeneration “cd” dog claim 5 , progressive rod-cone degeneration “prcd” dog claim 5 , early retinal degeneration “erd” dog claim 5 , rod-cone dysplasia 1 claim 5 , 2 & 3 “rcd1 claim 5 , rcd2 and rcd3” dogs claim 5 , photoreceptor dysplasia “pd” dog claim 5 , and Briard “RPE-65” dog.7. The method of claim 6 , wherein the outcome of the therapy in the animal model is evaluated using one or more of behavioral tests claim 6 , fluorescent angiography claim 6 , histology claim 6 , and functional testing such as measuring the ability of the cells to perform phagocytosis (photoreceptor fragments) claim 6 , vitamin A metabolism claim 6 , tight junctions conductivity claim 6 , or evaluation using electron microscopy.8. A method for the spontaneous differentiation ...

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Номер записи: 83
10-02-2022 дата публикации

A SERUM-FREE COMPLETE MEDIUM FOR INDUCING DIFFERENTIATION OF A MESENCHYMAL STEM CELL TO A CORNEAL EPITHELIAL CELL

Номер: US20220041982A1
Автор: CHEN Mengmeng, FU Xueqi, ZHANG Bingqiang, Zou Wei
Принадлежит:

A serum-free complete medium for inducing differentiation of a mesenchymal stem cell to a corneal epithelial cell in the field of differentiation induction of stem cells, prepared by the following method: uniformly mixing the serum-free complete medium, containing 5-10 μmol of resveratrol, 2-4 μmol of icariin, 1-3 nmol of aspirin, 1-3 nmol of parathyroid hormone, 5-10 nmol of hydrocortisone, 1-3 mg of rapamycin, 2-10 μg of testosterone, 2-10 μg of EPO, 2-10 μg of LIF and the balance of a corneal epithelial cell serum-free medium in per 1 L; and then performing sterilization by filtration. The disclosure uses resveratrol and icariin in combination with aspirin, parathyroid hormone, hydrocortisone, rapamycin, testosterone and growth factors to cooperatively induce directional differentiation, uses nontoxic induction components, is high in induction efficiency and short in induction time, and achieves high induced corneal epithelial cell activity, no cell transplantation rejection, no ethical problem and high safety. 1. A serum-free complete medium for inducing differentiation of a mesenchymal stem cell to a corneal epithelial cell , prepared by the following method: uniformly mixing the serum-free complete medium for differentiation induction , containing 5-10 μmol of resveratrol , 2-4 μmol of icariin , 1-3 nmol of aspirin , 1-3 nmol of parathyroid hormone , 5-10 nmol of hydrocortisone , 1-3 mg of rapamycin , 2-10 μg of testosterone , 2-10 μg of EPO , 2-10 μg of LIF and the balance of a corneal epithelial cell serum-free medium in per 1 L; and then performing sterilization by filtration.2. A serum-free complete medium for inducing differentiation of a mesenchymal stem cell to a corneal epithelial cell , prepared by the following method: uniformly mixing the serum-free complete medium for differentiation induction , containing 8 μmol of resveratrol , 3 μmol of icariin , 2 nmol of aspirin , 2 nmol of parathyroid hormone , 7 nmol of hydrocortisone , 2 mg of rapamycin , 7 ...

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Номер записи: 84
10-02-2022 дата публикации

GENERATION OF FUNCTIONAL AND PATIENT-SPECIFIC THYMIC TISSUE IN VIVO FROM INDUCED PLURIPOTENT STEM CELLS

Номер: US20220041988A1
Автор: Jimeno Antonio, Morton John Jason, Ramos Stephan A., Russ Holger A.
Принадлежит:

The disclosed technology includes methods, systems, and devices for generating patient-specific functional thymic epithelial progenitor (TEP) cells. In some implementations, a method may include generating iPSCs from HSC; causing differentiation of the iPSC into thymic epithelial progenitor (TEP) cells, generating thymic epithelial cells by transplantation of the TEP cells into a host, wherein the TEP cells may differentiate into mature functional thymic epithelial cells (TECs). In some implementations, a system may include a cell population of patient specific cells, a population of iPSCs, a culture system for differentiating the iPSCs into a population of patient-specific TEP cells for transfer to a host or the patient to allow the TEP cells to differentiate into mature, functional TEC. 1. A method for generating patient-specific thymic epithelial cells (TECs) , the method comprising: isolating a cell from the patient;administering one or more factors to the cell to reprogram the cell and create an induced pluripotent stem cell (iPSC);culturing the patient-specific iPSC for 9-14 days in a differentiation media to create a thymic epithelial progenitor (TEP) cell; andtransferring at least one TEP into a recipient; andallowing the TEP cell to differentiate into a TEC.2. The method of claim 1 , wherein the iPSC is derived from a hematopoietic stem cell (HSC) or peripheral blood mononuclear cell (PBMC).3. The method of claim 1 , wherein the TECs are mature claim 1 , functional claim 1 , patient-specific thymic epithelial cells (TEC).4. The method of claim 1 , further comprising the step of contacting a patient-derived T-cell with the TEC to produce a functional T-cell.5. The method of claim 1 , further comprising the step of contacting a patient-derived T-cell with the TEPs to produce a functional T-cell and or functional TECs.6. The method of any of - claim 1 , wherein the mature T-cell expresses one or more of CD69 claim 1 , CD25 claim 1 , CD5 claim 1 , CD7 claim 1 , ...

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Номер записи: 85
23-01-2020 дата публикации

METHODS FOR PRODUCTION OF PLATELETS FROM PLURIPOTENT STEM CELLS AND COMPOSITIONS THEREOF

Номер: US20200023011A1
Автор: Feng Qiang, Lanza Robert P., Lu Shi-Jiang
Принадлежит: Astellas Institute for Regenerative Medicine

Methods for production of platelets from pluripotent stem cells, such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are provided. These methods may be performed without forming embryoid bodies or clusters of pluripotent stem cells, and may be performed without the use of stromal inducer cells. Additionally, the yield and/or purity can be greater than has been reported for prior methods of producing platelets from pluripotent stem cells. Also provided are compositions and pharmaceutical preparations comprising platelets, preferably produced from pluripotent stem cells. 1. A pharmaceutical preparation that is suitable for use in a human patient comprising at least 10platelets , wherein the preparation is substantially free of leukocytes and wherein substantially all of the platelets are functional.26.-. (canceled)7. A bioreactor having weakly adherent or non-adherent megakaryocytes that produce functional platelets without feeder cells.8. A composition , a cryopreserved composition , or a bank comprising MLPs.913.-. (canceled)14. A method for producing platelets from megakaryocytes comprising:(a) providing a non-adherent culture of megakaryocytes;(b) contacting the megakaryocytes with (i) TPO or a TPO agonist, (ii) hematopoietic expansion medium and optionally TPO or a TPO agonist, SCF, IL-6 and IL-9, or (iii) hematopoietic expansion medium and optionally TPO or a TPO agonist, SCF, and IL-11 to cause the formation of proplatelets in culture, wherein the proplatelets release platelets; and(c) isolating the platelets.1535.-. (canceled)36. The method of claim 14 , wherein the megakaryocytes are generated by:(a) culturing pluripotent stem cells to form hemogenic endothelial cells (PVE-HE);(b) culturing the hemogenic endothelial cells to form MLPs; and(c) culturing the MLPs to form megakaryocytes.3750.-. (canceled)51. A method of treating a patient in need of platelet transfusion claim 1 , comprising administering to the patient the ...

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Номер записи: 86
24-01-2019 дата публикации

Chondrocyte Precursors Derived From Human Embryonic Stem Cells

Номер: US20190024053A1
Автор: Thies R. Scott
Принадлежит:

This invention provides a system for obtaining cells of the chondrocyte lineage by differentiating primate pluripotent stem cells. The process involves culturing the cells as a micromass or other aggregate form in a cocktail of differentiation agents that facilitates outgrowth of the desired cell type. Progeny are capable of synthesizing Type II collagen or aggrecan, or other products that are characteristic of the chondrocyte lineage. Chondrocytes and chondrocyte precursor cells obtained according to this disclosure are suitable for use in both research and clinical therapy. 1. A cell population obtained by differentiating primate pluripotent stem (pPS) cells , in which at least 5% of the cells synthesize either Type II collagen or aggrecan from an endogenous gene:2. The cell population of claim 1 , in which less than 1% of the cells synthesize elastin claim 1 , Type I collagen claim 1 , Type X collagen claim 1 , or osteocalcin.3. The cell population of claim 1 , which causes closure of a 6 mm hole within 2 months in the animal model described by Koppel et al. claim 1 , Biomaterials 22:1407 claim 1 , 2001.4. A population of chondrocyte progenitors that proliferates in an in vitro culture claim 1 , obtained by differentiating primate pluripotent stem (pPS) cells claim 1 , and capable of forming progeny having the characteristics of the cells of .5. The cell population of claim 1 , comprising less than 1% undifferentiated pPS cells.6. The cell population of claim 1 , comprising cells that have been genetically altered to express telomerase reverse transcriptase (TERT) at an elevated level.7. Two cell populations claim 1 , comprising the differentiated cell population of claim 1 , and the undifferentiated pPS cell line from which it was obtained.8. A method for obtaining the cell population of claim 1 , comprising differentiating the pPS cells claim 1 , then culturing the differentiated cells with a mixture of chondrocyte differentiation factors.9. The method of claim ...

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Номер записи: 87
23-01-2020 дата публикации

DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELLS

Номер: US20200024578A1
Автор: Rezania Alireza
Принадлежит: JANSSEN BIOTECH, INC.

The present invention provides methods to promote the differentiation of pluripotent stem cells and the products related to or resulting from such methods. In particular, the present invention provides an improved method for the formation of pancreatic hormone expressing cells and pancreatic hormone secreting cells. In addition, the present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer and the products related to or resulting from such methods. The present invention also provides methods to promote glucose-stimulated insulin secretion in insulin-producing cells derived from pluripotent stem cells. 1. A cell culture , comprising pancreatic endoderm cells , pancreatic endocrine cells , and an effective amount of inhibitor of TGF-βR-1 kinase.2. The cell culture of claim 1 , wherein the inhibitor of TGF-βR-1 kinase is an ALK5 inhibitor.3. The cell culture of claim 2 , wherein the ALK5 inhibitor is ALK5 inhibitor II or ALK5 inhibitor I.4. The cell culture of claim 1 , wherein there are more pancreatic endocrine cells than pancreatic endoderm cells in the cell culture.5. The cell culture of claim 1 , wherein the inhibitor of TGF-βR-1 kinase is (24346-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1 claim 1 ,5-naphthyridine) or [3-(Pyridin-2-yl)-4-(4-quinonyl)]-1H-pyrazole.6. The cell culture of claim 1 , wherein the cell culture comprises 0.1 μM to about 100 μM of the TGF-βR-1 kinase inhibitor.7. The cell culture of claim 1 , wherein the pancreatic endoderm cells and the pancreatic endocrine cells are derived from human embryonic stem cells.8. The cell culture of claim 1 , further comprising an effective amount of exendin-4 and/or an effective amount of a notch pathway inhibitor.9. The cell culture of claim 8 , wherein the cell culture comprises the notch pathway inhibitor claim 8 , and wherein the notch signaling pathway is a γ-secretase inhibitor.10. The cell culture of claim 9 , wherein the γ- ...

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Номер записи: 88
02-02-2017 дата публикации

DIFFERENTIATION OF STEM CELLS INTO THYROID TISSUE

Номер: US20170027994A1
Автор: Hollenberg Anthony N., Kotton Darrell, Kurmann Anita A., Serra Maria S.
Принадлежит:

Embodiments herein relate in vitro methods of stem cell differentiation into thyroid hormone producing cells and tissues, and methods of use of these cells. 1. An ex vivo or in vitro method for producing a thyroid follicular epithelial cell comprising: wherein the thyroid progenitor cell co-expresses a NK2 homeobox 1 (Nkx2-1) protein and a paired box 8 (Pax8) protein,', 'wherein the co-expression of Nkx2.1 and Pax8 are the products of endogenous genes within the cell, and the Nkx2.1 and Pax8 co-expressing thyroid progenitor cell does not comprise exogenously delivered nucleic acid sequences encoding for the co-expression of Nkx2.1 and Pax8 in the cell; and, 'a) culturing a thyroid progenitor cell in a differentiation medium under condition and time sufficient to further differentiate the thyroid progenitor cell along the thyroid lineage, wherein the differentiation medium comprising fibroblast growth factor 2 (basic) (FGF2),'} 'to produce a Nkx2-1+/Pax8+ co-expressing cell that also expresses early and mature thyroid markers: thyroglobulin (Tg+), thyroid stimulating hormone receptor (Tsh+), sodium iodine symporter (Nis+), and thyroid peroxidase (Tpo+).', 'b) then culturing the thyroid progenitor cell of step (a) in a maturation medium comprising dexamethasone and cAMP, or dexamethasone and thyroid stimulating hormone (TSH), or TSH, under condition and time sufficient'}2. The method according to claim 1 , wherein the thyroid progenitor cell is prepared by contacting an endodermal cell with a thyroid lineage culture medium to differentiate the endodermal cell into the thyroid lineage without exogenously delivered nucleic acid sequences resulting in the forced over-expression of the Nkx2-1 protein and the Pax8 protein in the endodermal cell claim 1 , thereby producing a Nkx2.1+ and Pax8+ thyroid progenitor cell claim 1 , wherein the thyroid lineage culture medium comprising:i) bone morphogenetic protein 4 (BMP4), andii) fibroblast growth factor 2 (basic) (FGF2),wherein ...

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Номер записи: 89
29-01-2015 дата публикации

Generation of Brown Adipose Tissue (BAT) from Mesenchymal Cells

Номер: US20150030662A1
Автор: Lee Michelle Hui Ching, Raghunath Michael, Sheppard Allan
Принадлежит:

Methods of generating functional human brown adipocytes, comprising exposing human stem cells, progenitor cells, or white adipocytes to culture with an differentiation cocktail that comprises one or more browning agents (e.g., one or more macromolecular crowders), and optionally one or more adipogenic agents, are described, as are populations of human brown adipocytes generated by the methods, and uses for the populations. Methods of generating functional human brown adipocytes in an individual, such as by administering a pharmaceutical composition comprising an differentiation cocktail, are also described. 1. A method of generating functional human brown adipocytes from human stem cells or progenitor cells , comprising culturing the cells with a differentiation cocktail comprising one or more adipogenic agents and one or more browning agents , wherein the cells thereby differentiate into functional human brown adipocytes.2. The method of claim 1 , wherein the human stem cells or progenitor cells are:a) derived from a mesenchymal or mesodermal lineage;b) cells that are capable of differentiating into cells from a mesenchymal or mesodermal lineage; orc) cells comprise cells selected from adipose-derived stem cells, human embryonic stem cells (HES), induced pluripotent stem cells (iPS), human bone marrow mesenchymal stem cells (hbmMSCs), preadipocytes, or progenitor cells found in adipose tissue or in skeletal muscle.34.-. (canceled)5. The method of claim 1 , wherein the one or more adipogenic agent(s) is selected from insulin claim 1 , glucocorticoid or synthetic equivalent claim 1 , a cAMP enhancer claim 1 , or vitamin C.6. The method of claim 1 , wherein the browning agent(s):a) comprises one or more maromolecular crowders; orb) further comprises an agent selected from thyroid hormone, a PPARγ receptor agonist, a bone morphogenetic protein, a retinoid, a cardiac natriuretic peptide, a myokine, a fibroblast growth factor, a microRNA, a lactogen, an insulin-like ...

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Номер записи: 90
29-01-2015 дата публикации

Optically sensitive cell network

Номер: US20150031070A1
Автор: Anat Marom, Sanjeev Kumar Mahto, Shy Shoham
Принадлежит: Technion Research and Development Foundation Ltd

A neural network is disclosed. The neural network comprises a plurality of optogenetically modified neural cells being three-dimensionally distributed in a hydrogel medium and being disconnected from any solid support having a shear modulus above 1 GPa.

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Номер записи: 91
01-02-2018 дата публикации

METHODS FOR MAKING AND USING SINOATRIAL NODE-LIKE PACEMAKER CARDIOMYOCYTES AND VENTRICULAR-LIKE CARDIOMYOCYTES

Номер: US20180028572A1
Автор: KELLER Gordon, PROTZE Stephanie
Принадлежит:

Provided are methods for producing compositions comprising a population of cardiomyocytes enriched for or substantially devoid of sinoatrial node-like pacemaker cardiomyocytes (SANLCM) from human pluripotent stem cells (hPSCs), and methods of use thereof. 2. The method of claim 1 , for producing a population of cardiomyocytes enriched for sinoatrial node-like pacemaker cardiomyocytes (SANLCM) claim 1 , the steps comprising:a. incubating cardiovascular mesoderm cells in a cardiac induction medium comprising a BMP component, optionally BMP4, above a selected amount, and retinoic acid (RA), and optionally one or more of a FGF inhibitor, a WNT inhibitor, optionally IWP2, VEGF and an activin/nodal inhibitor, optionally SB-431542; for a period of time to generate cardiovascular progenitor cells that express TBX18;b. incubating the cardiovascular progenitor cells in a basic medium comprising VEGF for a period of time to generate a population of cardiomyocytes enriched for SANLCMs; andc. optionally isolating the population of cardiomyocytes enriched for SANLCMs using a cardiomyocyte-specific surface marker or markers, optionally wherein the marker is signal-regulatory protein alpha (SIRPA) and/or the markers comprise SIRPA and THY-1/CD90 and the isolated population is enriched for SIRPApos CD90neg cells.3. The method of claim 2 , wherein the cardiovascular mesoderm cells are incubated with the FGF inhibitor and which FGF inhibitor is provided for all or part of a cardiac induction phase claim 2 , optionally added at day 2.5 claim 2 , day 3 or day 4 and before day 5.4. The method of claim 1 , for producing a population of cardiomyocytes substantially devoid of SANLCMs claim 1 , the method comprising:a. incubating cardiac progenitor cells in a cardiac induction medium comprising one or more of a WNT inhibitor, optionally IWP2, and VEGF; and optionally a FGF component and/or an activin/nodal inhibitor, optionally SB-431542; for a period of time to generate cardiovascular ...

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Номер записи: 92
02-02-2017 дата публикации

PROCESS FOR IMPLEMENTING IN VITRO SPERMATOGENESIS AND ASSOCIATED DEVICE

Номер: US20170029768A1
Автор: David Laurent, DURAND Philippe, PERRARD Marie-Hélène
Принадлежит:

The present invention relates to a process for in vitro spermatogenesis from male germinal tissue comprising conducting maturation of testicular tissue comprising germ cells in a bioreactor which is made of a biomaterial and comprises at least one cavity wherein the germinal tissue is placed, and recovering elongated spermatids and/or spermatozoa. 1. Method for in vitro spermatogenesis from male germinal tissue comprising conducting maturation of testicular tissue comprising germ cells in a bioreactor which is made of a biomaterial and comprises at least one cavity wherein the germinal tissue is placed , and recovering elongated spermatids and/or spermatozoa.2. Method according to claim 1 , wherein germinal tissue claim 1 , preferably testicular tissue claim 1 , comprises at least one seminiferous tubule or fragments of at least one seminiferous tubule claim 1 , preferably several seminiferous tubules or fragments of several seminiferous tubules.3. Method according to claim 2 , wherein the germinal tissue claim 2 , preferably testicular tissue claim 2 , comprises fragments from 2 to 50 claim 2 , 3 to 40 claim 2 , 4 to 30 claim 2 , 5 to 20 seminiferous tubules.4. Method according to claim 2 , wherein the tubules and/or fragments are obtained through mechanical separation or enzymatic separation of seminiferous tubules.5. Method according to claim 2 , wherein the fragments of seminiferous tubules have a size comprised between about 1 mm and about 5 mm.6. Method according to claim 1 , wherein the germinal tissue claim 1 , preferably testicular tissue claim 1 , comprises germ cells claim 1 , Sertoli cells and peritubular cells claim 1 , and optionally Leydig cells.7. Method according to claim 1 , wherein cells selected from the group consisting of germ cells claim 1 , Sertoli cells claim 1 , peritubular cells and mixtures thereof claim 1 , are added to the germinal tissue claim 1 , preferably testicular tissue.8. Method according to claim 1 , wherein the volume of the ...

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Номер записи: 93
02-02-2017 дата публикации

Anterior endoderm cells

Номер: US20170029769A1
Автор: "DAmour Kevin Allen", Agulnick Alan D., Baetge Emmanuel E., Eliazer Susan
Принадлежит: VIACYTE, INC.

Disclosed herein are cell cultures comprising PDX1-positive endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified PDX1-positive endoderm cells as well as methods for enriching, isolating and purifying, PDX1-positive endoderm cells to other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of endoderm cells, such as PDX1-positive foregut endoderm cells and PDX1-negative definitive endoderm cells, are also disclosed. 1109-. (canceled)110. An in vitro cell culture comprising human anterior endoderm cells and an effective amount of a retinoid.111. The in vitro cell culture of claim 110 , wherein the retinoid is retinoic acid (RA).112. The in vitro cell culture of claim 111 , wherein the RA is provided at a concentration of greater than 0.2 μM.113. The in vitro cell culture of claim 111 , wherein the RA is provided at a concentration ranging from about 0.2 μM to about 50 μM.114. The in vitro cell culture of claim 111 , wherein the RA is provided at a concentration of about 1 μM.115. The in vitro cell culture of claim 110 , wherein the human anterior endoderm cells are derived from human pluripotent cells.116. The in vitro cell culture of claim 110 , wherein the human anterior endoderm cells are derived from human definitive endoderm cells.117. The in vitro cell culture of claim 110 , wherein the human anterior endoderm cells express HOXA3.118. The in vitro cell culture of claim 110 , wherein the human anterior endoderm cells do not express alpha-fetoprotein claim 110 , CDX1 claim 110 , HOXC6 claim 110 , HOXA13 claim 110 , SOX1 or NFM.119. The in vitro cell culture of claim 110 , wherein the anterior endoderm cells are multipotent cells that can differentiate into pharynx claim 110 , lung claim 110 , esophagus or trachea cells.120. The in vitro cell culture of claim 110 , wherein the human anterior endoderm cells are differentiated from human ...

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Номер записи: 94
02-02-2017 дата публикации

SC-BETA CELLS AND COMPOSITIONS AND METHODS FOR GENERATING THE SAME

Номер: US20170029778A1
Автор: Fryer Benjamin, Gürtler Mads, Melton Douglas A., Millman Jeffrey R., Pagliuca Felicia J., PETERSON Quinn P., Rezania Alireza, Segel Michael Saris
Принадлежит:

Disclosed herein are methods, compositions, kits, and agents useful for inducing β cell maturation, and isolated populations of SC-β cells for use in various applications, such as cell therapy. 1339-. (canceled)340. A culture medium comprising a) Alk5 inhibitor , b) triiodothyronine (T3) , optionally c) staurosporine , and optionally d) CMRLS.341. A culture medium comprising a) KGF , b) SANT1) , and optionally c) RA , wherein the culture medium is substantially free of PdbU and LDN193189.3422. Use of the culture medium of claim to induce the in vitro differentiation of Pdx1-positive pancreatic progenitor cells into NKX6-1-positive pancreatic progenitor cells.343. A culture medium comprising a) TGF-β signaling pathway inhibitor , b) a TH pathway activator , and at least one additional β cell-maturation factor selected from the group consisting of i) XXI , ii) Betacellulin , iii) a low concentration of a RA signaling pathway activator , and iv) a SHH pathway inhibitor. This application claims the benefit of U.S. Provisional Application No. 61/833,898, filed on Jun. 11, 2013, and U.S. Provisional Application No. 61/972,212, filed on Mar. 28, 2014, the contents of which are hereby incorporated by reference in their entirety.Research to-date has generated only abnormally functioning insulin-expressing cells, which do not secrete appropriate amounts of insulin in response to sequentially varied glucose levels, or pancreatic progenitor cells that can only mature into functioning insulin-expressing cells after 3 months of transplantation into a mouse host (Cheng et, al., 2012; D′Amour et al., 2005; D′Amour et al., 2006; Kroon et al., 2008; Nostro et al., 2011; Rezania et al., 2012; Schulz et al., 2012; Xie et al., 2013). In contrast to normal islets or dispersed adult β cells, which release high levels of insulin in response to high levels of glucose in the “glucose stimulated insulin secretion” (GSIS) assay and can do so repeatedly, hPSC-derived insulin-expressing cells ...

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Номер записи: 95
30-01-2020 дата публикации

PANCREATIC ENDOCRINE CELLS AND METHODS THEREOF

Номер: US20200030383A1
Автор: XU JEAN
Принадлежит: JANSSEN BIOTECH, INC.

The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides an improved method for the formation of pancreatic endoderm, pancreatic hormone expressing cells and pancreatic hormone secreting cells. The present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer. 1. A method for generating human pancreatic endocrine cells , comprising differentiating pancreatic endoderm cells into pancreatic endocrine cells by culturing the pancreatic endoderm cells in a medium supplemented with a gamma secretase inhibitor , thereby generating pancreatic endocrine cells.2. The method of claim 1 , wherein the pancreatic endoderm cells are cultured with the gamma secretase inhibitor for about 1 to about 5 days.3. The method of claim 1 , wherein the pancreatic endoderm cells are cultured with the gamma secretase inhibitor for about 3 to about 5 days.4. The method of claim 1 , wherein the pancreatic endoderm cells are cultured with the gamma secretase inhibitor for about 3 days.5. The method of claim 1 , wherein the pancreatic endoderm cells are cultured with the gamma secretase inhibitor for about 5 days.6. The method of claim 1 , wherein the gamma secretase inhibitor is used at a concentration of about 0.1 μM to about 100 μM.7. The method of claim 6 , wherein the gamma secretase inhibitor is used at a concentration of about 10 μM.8. The method of claim 1 , wherein the gamma secretase inhibitor is 1S-Benzyl-4R-[1-(1S-carbamoyl-2-phenethylcarbamoyl)-1S -3-methylbutylcarbamoyl]-2R-hydrozy-5-phenylpentyl] carbamic Acid tert-butyl Ester (L-685 claim 1 ,458).9. The method of claim 8 , wherein L-685 claim 8 ,458 is used at a concentration of about 0.1 μM to about 100 μM.10. The method of claim 9 , wherein L-685 claim 9 ,458 is used at a concentration of about 10 μM.11. The method of claim 1 , wherein the pancreatic endoderm cells are ...

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Номер записи: 96
17-02-2022 дата публикации

EMBRYONIC ERYTHROBLAST-CONTAINING CELL POPULATION AND METHOD FOR PRODUCING SAME, CELL CULTURE COMPOSITION, AND COMPOUND TEST METHOD

Номер: US20220049220A1
Автор: Asano Kouji
Принадлежит: Sumitomo Chemical Company, Limited

Provided is a method for producing a cell population containing embryonic erythroblasts, including the steps of: (1) subjecting pluripotent stem cells to suspension culture to form a cell aggregate; and (2) obtaining the cell population from the cell aggregate obtained in step (1), step (2) including step (2a) of subjecting the cell aggregate to adhesion culture. In addition, provided are an embryonic erythroblast-containing cell population, a cell culture composition containing the cell population, and a compound test method that uses the embryonic erythroblast-containing cell population. 137-. (canceled)38. A method for producing a cell population containing embryonic erythroblasts , comprising:(1) subjecting pluripotent stem cells to suspension culture to form a cell aggregate;(2) obtaining the cell population from the cell aggregate obtained in step (1),wherein step (2) comprises step (2a) of subjecting the cell aggregate to adhesion culture.39. The production method according to claim 38 , wherein step (2) further comprises step (2b) of collecting the cell population.40. The production method according to claim 38 , wherein at least 70% of cells included in the cell population are the embryonic erythroblasts.41. The production method according to claim 38 , wherein at least 50% of β-globin gene family expressed in cells of the cell population is ε-globin gene.42. The production method according to claim 38 , wherein step (1) is carried out using non-cell-adherent cultureware.43. The production method according to claim 38 , wherein step (2a) is carried out using cell-adherent cultureware or in the presence of feeder cells.44. The production method according to claim 43 , wherein the feeder cells are bone marrow stromal cells or a bone marrow stromal cell-derived cell line.45. The production method according to claim 38 , wherein step (1) follows a step of dispersing the pluripotent stem cells.46. The production method according to claim 38 , wherein step (1) ...

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Номер записи: 97
31-01-2019 дата публикации

Differentiation of pluripotent stem cells to form renal organoids

Номер: US20190032020A1
Автор: Melissa Little, Minoru TAKASATO
Принадлежит: University of Queensland UQ

A method is provided for producing renal organoids comprising nephrons, ureteric bud and vasculature and/or progenitors of these. In one embodiment, the methods includes contacting intermediate mesoderm cells with: fibroblast growth factor 9 and/or fibroblast growth factor 20 and/or fibroblast growth factor 2 and optionally, one or more selected from the group consisting of: bone morphogenic protein 7; heparin; a Wnt agonist; retinoic acid; and an RA antagonist under conditions that promote formation of vascularized renal organoids. Another embodiment includes producing mesoderm cells by sequentially contacting pluripotent stem cells with a Wnt agonist and fibroblast growth factor 9 and/or fibroblast growth factor 20 and/or fibroblast growth factor 2, followed by a relatively short re-exposure to the Wnt agonist. The renal organoids may have end uses such as for kidney repair and re generation, bioprinting of kidneys or functional components thereof, renal cell arrays and screening compounds for nephrotoxicity.

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Номер записи: 98
30-01-2020 дата публикации

METHODS AND COMPOSITIONS FOR PRODUCTION OF FALLOPIAN TUBE EPITHELIUM

Номер: US20200032215A1
Автор: Holzapfel Marie, Karlan Beth Y., Svendsen Clive N., Vogel Tilley Jenkins, Yucer Nur
Принадлежит: CEDARS-SINAI MEDICAL CENTER

The fallopian tube epithelium (FTE) has been recognized as a site of origin of high-grade serous ovarian cancer (HGSC). However, absence of relevant in vitro human models that can recapitulate tissue-specific architecture has hindered understanding of FTE transformation and initiation of HGSC. Here, induced pluripotent stem cells (iPSCs) were used to establish a novel 3-dimensional (3D) human FTE organoid in vitro model containing the relevant cell types of the human fallopian tube as well as a luminal architecture that closely reflects the organization of fallopian tissues in vivo. Modulation of Wnt and nodal/activin signaling pathways provided iPSC differentiation into Müllerian cells and subsequent use of pro-Müllerian growth factors promoted FTE precursors. The expression of Müllerian markers verified correct cellular differentiation. An innovative 3D growth platform, which enabled the FTE organoid to self-organize into a convoluted luminal structure, permitted final differentiation to a FTE lineage. This powerful human-derived FTE organoid model can be used to study the earliest stages of HGSC development and to identify novel and specific biomarkers of early fallopian tube epithelial cell transformation. 1. A method for generating a fallopian tube epithelium (FTE) , comprising:providing a quantity of human pluripotent stem cells (hPSCs);culturing the hPSCs in the presence of at least one first growth factor and at least one induction molecule to generate mesoderm cells;further culturing the mesoderm cells in the presence of at least one second growth factor, at least one second induction molecule, and at least first one kinase inhibitor to generate intermediate mesoderm (IM) cells;additionally culturing the IM cells in the presence of at least one third growth factor, and at least one second kinase inhibitor to generate Mullerian epithelium cells; anddifferentiating Mullerian epithelium cells by addition of at least one fourth growth factor into FTE.2. The ...

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Номер записи: 99
04-02-2021 дата публикации

MATURATION OF MAMMALIAN HEPATOCYTES

Номер: US20210032593A1
Автор: KÜPPERS-MUNTHER Barbara
Принадлежит: Takara Bio Europe AB

Directed differentiation and maturation of mammalian hepatocytes, such as human hepatocytes. The hepatocyte obtained show a phenotype which is more similar to that of primary hepatocytes than previously shown. In particular, exposure of mammalian hepatocytes, such as human hepatocytes, to at least one maturation factor selected from the group consisting of Src kinase inhibitors, vitamin D including precursors, metabolites and analogs thereof, hypoxia inducing compounds, sphingosine and sphingosine derivatives, activators of peroxisome proliferator-activated receptors (PPARs), platelet-activating factor (PAF), PKC inhibitors, and combinations thereof. 1. A method for producing mammalian hepatocytes , the method comprising:culturing mammalian hepatic progenitor cells under differentiation conditions to obtain hepatocytes, andexposing said hepatocytes to at least one hypoxia inducing compound selected from the group consisting of RAR-related orphan receptor alpha (ROR-alpha) ligands, CoCl2, and NaN3, optionally in combination with at least one maturation factor selected from the group consisting of Src kinase inhibitor, vitamin D including precursors, metabolites and analogs thereof, sphingosine and sphingosine derivatives, activators of peroxisome proliferator-activated receptors (PPARs), platelet-activating factor (PAF), and PKC inhibitors.2. The method according to claim 1 , further comprising initially culturing cells of the definitive endoderm (DE) under differentiation conditions to obtain said hepatic progenitor cells claim 1 , or further comprising initially culturing mammalian pluripotent stem (PS) cells under differentiation conditions to obtain cells of the definitive endoderm (DE cells) and further culturing the obtained cells under differentiation conditions to obtain said hepatic progenitor cells.3. The method according to claim 1 , wherein said mammalian cells are human cells.4. The method according to claim 1 , wherein said mammalian hepatocytes are ...

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Номер записи: 100