СПОСОБ ИНГИБИРОВАНИЯ РАДИАЦИОННО-ИНДУЦИРОВАННОГО УВЕЛИЧЕНИЯ КОЛИЧЕСТВА СТВОЛОВЫХ КЛЕТОК РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ ЧЕЛОВЕКА

Изобретение относится к области медицины, в частности к онкологии, и может быть использовано для ингибирования радиационно-индуцированного увеличения количества CD44+СD24-/low опухолевых стволовых клеток (ОСК). ОСК рака молочной железы человека инкубируют 24 часа до облучения и 48 часов после с водорастворимыми димерными бисбензимидазолами серии DBPA(n) с 1 или 4 метиленовыми группами в составе линкера DBPA, после чего регистрируют снижение радиационно-индуцированного увеличения количества CD44+CD24-/lowОСК, которые являются более радио- и химиорезистентными по сравнению с остальными опухолевыми клетками, а также снижение радиационно-индуцированной экспрессии виментина, который является маркером эпителиально-мезенхимального перехода, обеспечивающего формирование пула ОСК после облучения. Способ позволяет активировать в клетках злокачественных новообразований ряд сигнальных путей и может стать новым инструментом в борьбе со злокачественными новообразованиями. 3 ил., 3 пр.

СПОСОБ НАПРАВЛЕННОГО ТРАНСПОРТА БИОЛОГИЧЕСКИ АКТИВНЫХ ВЕЩЕСТВ И ПРИМЕНЕНИЕ СТВОЛОВЫХ КЛЕТОК ДЛЯ ИХ НАПРАВЛЕННОГО ТРАНСПОРТА

Изобретение относится к области биотехнологии и может быть использовано для направленного транспорта биологически активных веществ (БАВ). Проводят добавление БАВ к эмульсии перфторуглеродов (ПФУ), включающей по крайней мере: перфтордекалин и/или перфторметилциклогексилпиперидин, и/или перфтортрибутиламин, и/или перфтороктилбромид, стабилизированных раствором проксанола и/или фосфолипидами. Добавляют эмульсию ПФУ с БАВ к стволовым клеткам (СК) и проводят их совместное культивирование. После культивирования СК вводят субъекту, нуждающемуся во введении БАВ. Изобретение позволяет осуществлять направленный транспорт БАВ в организме. 2 н. и 14 з.п. ф-лы, 7 ил., 1 табл.

СПОСОБ ИНДУКЦИИ НАПРАВЛЕННОЙ ДИФФЕРЕНЦИРОВКИ МУЛЬТИПОТЕНТНЫХ ПРОГЕНИТОРНЫХ КЛЕТОК ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ В ИНСУЛИН-ПРОДУЦИРУЮЩИЕ β-КЛЕТКИ ПРИ САХАРНОМ ДИАБЕТЕ

Способ индукции дифференцировки мультипотентных прогениторных клеток поджелудочной железы в инсулин-продуцирующие β-клетки при сахарном диабете I типа, характеризующийся тем, что выделяют взвесь неадгезирующих мононуклеаров клеток из ткани поджелудочной железы при сахарном диабете, в полученной взвеси оценивают количество мультипотентных прогениторных клеток, олигопотентных прогениторных клеток и инсулин-продуцирующих β-клеток, затем в течение 30 дней в присутствии ростовых факторов: 4 нг/мл эпидермального фактора роста и 10 нг/мл фактора роста гепатоцитов, наращивают клеточную массу мультипотентных прогениторных клеток, по окончании цикла культивирования индуцируют дифференцировку полученных in vitro мультипотентных прогениторных клеток, характеризующихся CD45TER119, c-Kit, Flk-1, в β-клетки глюкагон-подобным пептидом GLP-1 в концентрации 6,7 мкл/мл.

Ноотропная композиция на основе полипептидных комплексов, выделенных из нейрональных прогениторных клеток в условиях гипоксии, и способ ее получения

Изобретение относится к области биохимии, в частности к способу получения ноотропной композиции на основе полипептидных комплексов, выделенных из нейрональных прогениторных клеток в условиях гипоксии, а также к ноотропной композиции на основе полипептидных комплексов, выделенных из нейрональных прогениторных клеток в условиях гипоксии. Указанная композиция характеризуется тем, что в ее состав входят белки и полипептиды с молекулярной массой от 5 кДа до 250 кДа, мозговой нейротрофический фактор (BDNF) не менее 130 пг/мл и глиального нейротрофического фактора (GDNF) не менее 30 пг/мл, фактор роста эндотелия сосудов (VEGF) не менее 90 пг/мл, суммарная масса белка не менее 1 мг/мл препарата. При этом клеточная культура нейрональных прогениторных клеток, из которой получают композицию, демонстрирует экспрессию нейронального β - тубулина III, молекулы адгезии нервных клеток (PSA-NCAM) и состоит из 95±5% TUBB3+ - клеток. Изобретение позволяет эффективно получать белково-пептидную композицию, в ...

СПОСОБ ИНГИБИРОВАНИЯ РАДИАЦИОННО-ИНДУЦИРОВАННОГО УВЕЛИЧЕНИЯ КОЛИЧЕСТВА СТВОЛОВЫХ КЛЕТОК РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ ЧЕЛОВЕКА

VERFAHREN ZUR DIFFERENZIERUNG MESENCHYMALER STAMMZELLEN ZU STEROIDPRODUZIERENDEN ZELLEN

Prostate stem cell

CELL FUSION PROMOTER AND ITS USE

Methods of determining therapies based on single cell characterization of circulating tumor cells (CTCs) in metastatic disease

Methods and materials for hematoendothelial differentiation of human pluripotent stem cells under defined conditions

Methods and compositions for differentiating pluripotent stem cells into cells of endothelial and hematopoietic lineages are disclosed.

Peripheral zone tumor cells, methods for their preparation and use

Method for culturing a subpopulation of circulating epithelial tumour cells from a body fluid

The invention relates to a method for culturing a subpopulation of circulating epithelial tumour cells from a body fluid of a human or animal suffering from an epithelial tumour, wherein cells contained in the body fluid each containing at least one cell nucleus are separated from the body fluid and cultured over at least 24 hours in suspension, with formation of spheroids.

ISOLATION AND USE OF SOLID TUMOR STEM CELLS

... ²²²A small percentage of cells within an established solid tumor have the ²properties of stem cells. These solid tumor stem cells give rise both to more ²tumor stem cells and to the majority of cells in the tumor that have lost the ²capacity for extensive proliferation and the ability to give rise to new ²tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell ²progeny arising from a solid tumor stem cell. We have developed a xenograft ²model in which we have been able to establish tumors from primary tumors via ²injection of tumors in the mammary gland of severely immunodeficient mice. ²These xenograft assay have allowed us to do biological and molecular assays to ²characterize clonogenic solid tumor stem cells. We have also developed ²evidence that strongly implicates the Notch pathway, especially Notch 4, as ²playing a central pathway in carcinogenesis.² ...

METHODS FOR ENHANCING LIFESPAN AND/OR TREATING CELLULAR PROLIFERATIVE DISORDERS BY TRANSPLANTATION

The invention found that first, the feasibility of transfer of tumor resistance and other healthy longevity characters through transplantation of bone marrow mononuclear cells (BMMNC) or hematopoietic stem cells (HSC)/hematopoietic stem and progenitor cells (HSPC) consisting of genetically engineered EKLF gene encoding the hematopoietic transcription factor EKLF. Secondly, the present invention demonstrates expression of EKLF in the long-term hematopoietic stem cells (LT-HSC), and thus EKLF as a target of regulation of hematopoiesis.

METHOD FOR ISOLATING AND DETECTING CANCER STEM CELLS

La présente invention porte sur l'utilisation in vitro d'au moins une lectine reconnaissant le motif fucose alpha 1-2 galactose pour le marquage de cellules souches cancéreuses d'organes impliqués dans la respiration pour obtenir des cellules souches cancéreuses d'organes impliqués dans la respiration marquées, dans un échantillon biologique. Dans un mode de réalisation particulier, ladite au moins une lectine est choisie parmi les lectines Ulex Europaeus agglutinin 1 (UEA-1) ou son homologue Trichosanthes japonica agglutinin II (TJA-II), Agaricus Bisporus agglutinin (ABA), Amaranthus Caudatus agglutinin (ACA), jacaline, Griffonia Simplicifolia lectin I (GSL-I) et Griffonia Simplicifolia lectin II (GSL-II). Dans un mode de réalisation particulier, ledit organe impliqué dans la respiration est choisi parmi les poumons, le larynx, le pharynx, la bouche, le nez, la gorge, la langue, les sinus, la trachée et les glandes salivaires comprenant les amygdales et la glande parotide.

COMPOSITIONS ENRICHED IN NEOPLASTIC STEM CELLS AND METHODS COMPRISING SAME

A neoplastic stem cell population enriched for expression of the OCT4 tra nscription factor as well as methods for their identification, isolation and enrichment are described. The OCT4-enriched neoplastic stem cell population is further utilized for the induction and analysis of cancer in an animal. In addition, methods of preventing, abrogating, or inhibiting cancer, tumor growth, and metastasis via OCT4 inhibition are further provided.

NOVEL MEDULLOBLASTOMA-FORMING CELL LINE

Isolated medulloblastoma-forming clonogenic cells are provided which are useful to form stable cell lines as well as a non-human animal models of medulloblastoma th at mimic human medulloblastoma, thereby providing a means to screen for candidate therapeutic compounds.

CANCER STEM CELLS AND USES THEREOF

Disclosed are enriched preparations of neuroblastoma tumor initiating cells (NB TICs). The NB TICs are capable of self-renewal, initiating neuroblastoma tumor growth in vivo and are capable of being passaged in high frequency. These NB TICs have chromosomal abnormalities and are capable of giving rise to secondary tumor spheres. Methods are also disclosed for preparing the enriched preparations of NB TICs, such as from neuroblastoma tumor tissue and metastasized bone marrow. Also disclosed are methods of screening candidate substances to identify therapeutic agents for the treatment of neuroblastoma. Methods are also provided for screening a sample for neuroblastoma, as well as for screening a sample to identify the stage of neuroblastoma present. Kits are also provided for selecting appropriate anti-neuroblastoma compounds for a patient, and utilize isolated compositions of the patients' neuroblastoma tumor initiating cells. In this manner, a customized medicinal profile for the patient ...

COMPOSITIONS AND METHODS FOR TREATING AND DIAGNOSING CANCER

The present invention relates to compositions and methods for characterizing, treating and diagnosing cancer. In particular, the present invention provides a cancer stem cell profile, as well as novel stem cell cancer markers useful for the diagnosis, characterization, prognosis and treatment of cancer and in particular the targeting of solid tumor stem cells.

METHODS AND MEANS RELATED TO CANCER STEM CELLS

This invention relates to the methods for the identification and isolation of cancer stem cells from cultured cancer cell lines. Cell line-derived cancer stem cells isolated using the present methods may be useful, for example, in assays to screen compounds for anti-cancer stem cell activity and in target discovery methods for identifying novel expressed genes and druggable targets. The invention also relates to the screening of compounds for activity against cell line-derived cancer stem cells.

ISOLATION OF NON-EMBRYONIC STEM CELLS AND USES THEREOF

The invention described herein relates to methods of isolating non-embryonic stem cell, e.g., adult stem cell, from a non-embryonic tissue, e.g., an adult tissue or organ. Non- embryonic stem cells (e.g., adult stem cells) thus isolated from the various tissues or organs can self-renew or propagate indefinitely in vitro, are multipotent and can differentiate into the various differentiated cell types normally found within the tissue or organ from which the stem cells are isolated. In addition, the isolated stem cells can be propagated through clonal expansion of a single isolated stem cell, to produce a clone of which at least about 40%, 70%, or 90% or more cells within the clone can be further passaged as single cell originated clones.

IMMORTALIZATION OF EPITHELIAL CELLS AND METHODS OF USE

The present invention is directed towards methods of culturing non-keratinocyte epithelial cells, with the methods comprising culturing non-keratinocyte epithelial cells in the presence of feeder cells and a calcium-containing medium while inhibiting the activity of Rho kinase (ROCK) in the feeder cell, the non-keratinocyte epithelial cells or both during culturing.

IN VITRO CULTURE CONDITIONS FOR T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA

We describe cell culture media for in vitro culture of a human cancer cell of the lymphocyte lineage (e.g., leukemia, lymphoma, or other blasts) or a precursor thereof, especially T-cell acute lymphoblastic leukemia / lymphoma (T-ALL), as well as methods for at least maintenance, propagation, or both of the human cancer cell or its precursor.

METHOD FOR THE ISOLATION FOR MAMMALIAN STEM CELLS AND USES THEREOF

The present invention concerns the field of stem cell biology, and in particular relates to a method for producing an isolated bona fide population of mammalian stem cells, and uses of the stem cells thus produced. Human glioblastomas (hGBMs) have now been shown to contain a minor subset of cells bearing the defining features of somatic stem cells (SCs) and the ability to establish, expand and perpetuate these tumors. They are defined stem-like tumor propagating cells (TPCs). This has caused a paradigmatic shift in the way we interpret hGBM physiology, for it identifies TPCs as a major culprit to be tackled for the development of novel therapeutics. It also suggests that studying the regulatory mechanisms of normal neurogenesis may point to specific inhibitors of TPCs.

A method for utilizing the human esophageal squamous cell ball culture concentrates the cancer stem cells

Method for enriching tumor stem cells through continuous low dose radiation

The invention relates to a method for enriching tumor stem cells through continuous low dose radiation. The method comprises the following steps: culturing cancer cell lines, carrying out low dose radiation, carrying out the low dose radiation again after culturing for a period of time, radiating for N times in total to enrich the tumor stem cells in the cell lines and increase the ratio of the tumor stem cells, wherein the cancer cell lines are breast cancer cell lines preferably; 60 Co is preferably adopted to carry out the low dose radiation; the low dose is 1.5-3Gy preferably and 2Gy more preferably; the culturing time is 1-2 weeks preferably; and the radiating times in total is 3 preferably. The method for enriching the tumor stem cells, provided by the invention, is very simple and practical and a new way is developed for the follow-up further study of the characteristics of the tumor stem cells.

Method for enriching and streaming human ovarian cancer stem cells

Method for identifying, separating and culturing lymphoma stem cells from non-Hodgkin lymphoma cell line

NICHE TARGETING OF QUIESCENT CANCER STEM CELLS

The disclosure provides methods for determining the self-renewal potential of a cancer stem cell (CSC), or for predicting the drugability (susceptibility to a drug) of a CSC, and/or for predicting the progression of a cancer that corresponds to the CSC. In alternative embodiments, the disclosure provides methods for determining whether a CSC in a niche is more pro-apoptotic or more anti-apoptotic in relation to a normal stem cell or a CSC from another niche. In alternative embodiments, the disclosure provides methods for determining the prognosis or malignant potential of a cancer. In alternative embodiments, the disclosure provides methods determining the anti-apoptotic versus a pro-apoptotic potential of a cancer stem cell (CSC).

SINGLE BLADDER CELL-DERIVED ORGANOIDS

The present invention relates to organoids derived from a single cell, such as a bladder cancer cell, and methods and compositions relating to the production and use thereof, including cell culture medium for producing organoids and methods of personalized treatment for bladder cancer and Interstitial cystitis (IC) or painful bladder syndrome (PBS). The invention further provides a humanized mouse including a bladder organoid derived from a patient's bladder cell.

METHOD FOR ISOLATING CANCER STEM CELLS

The invention relates to the use of a lectin that recognises the fucose α 1-2 galactose unit, as a first means for labelling and optionally a second means for labelling colorectal cancer stem cells, in particular a lectin that recognises the T antigen, in order to carry out a method for the detection and optionally isolation of colorectal cancer stem cells, a method for the detection and optionally isolation of colorectal cancer stem cells for research purposes, and a method for the in vitro diagnosis of colorectal cancer recurrence risk and/or aggressiveness so as to define a prognostic value in order to make colorectal cancer therapy adjustments, as well as a kit comprising a lectin that recognises the fucose α 1-2 galactose unit and a lectin that recognises the T antigen.

HLA-INDEXED REPOSITORY OF IPSCS AND IPSC-DERIVED STEM CELLS, AND RELATED SYSTEMS AND METHODS

Described herein is a managed, indexed repository of hematopoietic stem cell (HSC) lines and/or blood progenitor cell lines derived from induced pluripotent stem cells (iPSCs) (or embryoid bodies formed from iPSCs), wherein each of the HSC lines, blood progenitor cell lines, embryoid bodies, and/or iPSC lines has corresponding data comprising a set of characterized HLA loci, said corresponding data being stored in a searchable database for retrieval of one or more matching physical cell lines upon query. The repository comprises an HLA-indexed bank of iPSCs, embryoid bodies, HSCs, and/or blood progenitor cells for each of a set of HLA types, for identification and provision of allogeneic cell lines suitable for transplantation to reestablish hematopoietic function in patients with damaged, diseased, or otherwise abnormal bone marrow and/or immune system.

CARDIAC STEM CELLS AND METHODS OF IDENTIFYING AND USING THE SAME

Methods of isolating cardiac cells, including cardiac cells capable of regenerating cardiac tissue are provided. Compositions comprising cardiac cells, including cardiac cells capable of regenerating cardiac tissue are also provided. Methods of using cardiac cells, cardiac progenitor cells, including cardiac cells capable of regenerating cardiac tissue, are provided. Methods of identifying the prognosis of patients treated for heart disease and/or methods of predicting the regeneration of cardiac cells in a subject are also provided.

Composition for inducing dedifferentiation into cancer stem cells comprising ribosome-activating inhibitor as active ingredient, cancer organoid culture method and anticancer drug screening platform based thereon

A composition for inducing dedifferentiation from cancer cells to cancer stem cells comprising a ribosome-activating inhibitor as an active ingredient, a method of culturing a cancer organoid based thereon and an anticancer drug screening platform, and the increase of colorectal cancer stem cell group induced by the exposure of ribosome-inactivating stress was regulated by the ATF3 gene.

METHODS FOR ENHANCING LIFESPAN AND/OR TREATING CELLULAR PROLIFERATIVE DISORDERS BY TRANSPLANTATION

INFECTIOUS DISEASE MOUSE MODELS

ПРЕПАРАТ СТВОЛОВЫХ КЛЕТОК С РЕПРОГРАММИРОВАННЫМ КЛЕТОЧНЫМ СИГНАЛИНГОМ, СПОСОБ ПОЛУЧЕНИЯ ЭТОГО ПРЕПАРАТА И ЕГО ПРИМЕНЕНИЕ

Изобретение относится к области медицины и касается препарата стволовых клеток (СК) с репрограммированным клеточным сигналингом, способа получения этого препарата и его применения. Сущность изобретения включает препарат СК с репрограммированным клеточным сигналингом, содержащий базовый препарат СК, в мембрану, и/или ядро, и/или цитоплазму которых имплантирован способный к регулированию сигнальных путей СК и клеток патологического очага в организме млекопитающего белковый или фармацевтический препарат, предварительно инкапсулированный в наноконтейнеры размером до 100 нм, полученные из биодеградируемого материала, интактного для органелл и компартаментов СК базового препарата. Этот материал имеет заданные сроки биодеградации в организме млекопитающего для обеспечения программируемого выхода белкового или фармацевтического препарата во внутри- или межклеточное пространство и осуществления тем самым перепрограммирования сигнальной трансдукции ключевых генов СК в требуемом терапевтическом направлении ...

Ноотропная композиция на основе полипептидных комплексов, выделенных из глиальных прогениторных клеток в условиях теплового шока, и способ её получения

Изобретение относится к получению ноотропной композиции на основе полипептидных комплексов, выделенных из глиальных прогениторных клеток в условиях теплового шока. Способ включает забор биоптата кожи, получение культуры фибробластов, криоконсервацию культуры фибробластов, размораживание культуры фибробластов, адаптирование культуры фибробластов к xeno free условиям культивирования, репрограммирование фибробластов для получения индуцированных плюрипотентных стволовых клеток (ИПСК), культивирование ИПСК, криоконсервацию ИПСК, размораживание ИПСК, дифференцировку ИПСК в глиальные прогениторные клетки, культивирование глиальных прогениторных клеток в условиях теплового шока, сбор кондиционированной среды и получение белково-пептидного комплекса. Для моделирования теплового шока глиальные предшественники культивируют в течение часа при 40°С в ростовой среде, содержащей DMEM/F12, 2% добавки В27, 20 нг/мл FGF-2, 1 мкМ пурморфамин, после чего производят замену среды на DMEM/F12 и культивируют в ...

СПОСОБ ОБНАРУЖЕНИЯ ИЛИ ВЫДЕЛЕНИЯ/ПОЛУЧЕНИЯ ЦИРКУЛИРУЮЩЕЙ ОПУХОЛЕВОЙ КЛЕТКИ, ИСПОЛЬЗУЮЩИЙ МЕТОД ПРОЛИФЕРАЦИИ КЛЕТОК

Изобретение относится к медицине, а именно к способу обнаружения циркулирующей опухолевой клетки и/или циркулирующей опухолевой стволовой клетки из биологической циркулирующей жидкости организма. Способ включает этап предварительной обработки образца биологической циркулирующей жидкости организма для получения фазы мононуклеарных клеток, в котором предварительная обработка образца биологической циркулирующей жидкости организма с удалением жидкого компонента и неклеточного компонента, содержащегося в биологической циркулирующей жидкости организма; этап получения луночного планшета, в который введена культуральная среда, содержащая бессывороточную ростовую среду для циркулирующей опухолевой клетки и/или циркулирующей опухолевой стволовой клетки, и посева в него мононуклеарных клеток, полученных на первом этапе, с последующей инкубацией; этап удаления культуральной среды из лунки планшета, полученного путем инкубации на втором этапе; а также этап обнаружения адгезивной опухолевой клетки, прикрепленной ...

СПОСОБ НАПРАВЛЕННОГО ТРАНСПОРТА БИОЛОГИЧЕСКИ АКТИВНЫХ ВЕЩЕСТВ И ПРИМЕНЕНИЕ СТВОЛОВЫХ КЛЕТОК ДЛЯ ИХ НАПРАВЛЕННОГО ТРАНСПОРТА

... 1. Способ направленного транспорта биологических активных веществ (БАВ) у субъекта, нуждающегося во введении БАВ, включающий следующие этапы: ! а) проводят добавление БАВ к эмульсии перфторуглеродов (ПФУ), включающей по крайней мере: перфтордекалин, и/или перфторметилциклогексилпиперидина, и/или перфтортрибутиламина, и/или перфтороктилбромида, стабилизированных раствором проксанола и/или фосфолипидами; ! б) добавляют эмульсию ПФУ с БАВ к стволовым клеткам (СК) и проводят их совместное культивирование; ! в) осуществляют введение СК после культивирования субъекту, нуждающемуся во введении БАВ. ! 2. Способ по п.1, отличающийся тем, что в качестве субъекта выступает млекопитающее. ! 3. Способ по п.2, отличающийся тем, что в качестве млекопитающего выступает человек. ! 4. Способ по п.1, отличающийся тем, что ПФУ эмульсия состоит из смеси перфторуглеродов: перфтордекалина, перфторметилциклогексилпипередина, перфтортрибутиламина и перфтороктилбромида в соотношении 9:1:0,01:0,01 об.%, стабилизированных ...

Prostate cancer stem cells

SPECIFIC CD4+CD25+-REGULATORI T-CELLS FOR HÄMATOPOETI ZELLTRANSPLANTATION AND IMMUNE TOLERANCE

CANCER PROSTATA MAIN CELL

Identification, isolation and elimination of cancer stem cells

Compositions and methods for treating and diagnosing cancer

Methods of treating minimal residual cancer

Disclosed herein are methods of treating minimal residual cancer in a subject. The methods involve contacting disseminated cancer cells (DCCs) in a subject with a bone morphogenic protein 7 (BMP7) derivative protein, where the contacting induces or maintains dormancy in the contacted DCCs of the subject to treat minimal residual cancer in the subject. Also disclosed are methods that involve contacting DCCs in a subject with a protein kinase RNA-like endoplasmic reticulum kinase (PERK) inhibitor selected from LY2, LY3, and LY4, where said contacting eradicates DCCs in the subject to treat minimal residual cancer in the subject.

Methods for identifying, purifying and enriching immature or stem cancer-initiating cells from tumors and use thereof

Methods for identifying, purifying and enriching immature or stem cancer-initiating cells from tumors and use thereof

... 42 Abstract of the invention: The present invention is related to methods for the preparation of cell compositions, isolated compositions obtainable therefrom, related isolated cell compositions, kits and use thereof. More specifically, the present invention provides a method for identifying, purifying and enriching immature or stem cancer-initiating cells in a 5 sample. The cell compositions, related methods and uses according to the present invention are useful in the treatment of cancers and/or the detection of enriching immature or stem cancer-initiating cells, notably cancers of the central and peripheral nervous system, metastasis to the brain.

Compositions and methods for treating and diagnosing cancer

COMPOSITIONS AND METHODS FOR TREATING AND DIAGNOSING CANCER Abstract The present invention relates to compositions and methods for treating, characterizing, and diagnosing cancer. In particular, the present invention provides gene expression profiles associated with solid tumor stem cells, as well as novel stem cell cancer markers useful for the diagnosis, characterization, and treatment of solid tumor stem cells.

Improvements in Oligodendroglial cell culturing methods and in methods for treating neurodegenerative disorders by using thyroid hormones or analogues

The present invention relates to methods of treating or ameliorating certain neurodegenerative disorders (namely, dysmyelinating and demyelinating disorders) in patients in need of such treatment or amelioration. The invention provides methods of treating or ameliorating a patient in need of such treatment, comprising the administration to the patient of: (a) thyroid hormones or thyroid hormone analogues; (b) cell replacement therapies involving the use of homogenous Oligodendrocyte Precursor Cells derived from embryonic stem cells that have been treated with thyroid hormones or thyroid hormone analogues; (c) gene therapy to correct mutated genes in vivo; or (d) a combination of two or more of (a), (b) and (c). The invention also provides compositions and formulations of thyroid hormones and thyroid hormone analogues for use in treating or ameliorating such disorders.

Compositions and methods for programming adult cells with platelet rich fraction of blood containing platelet-like cells

The described invention provides a method of functionally reprogramming adult cells to an immature cell type that expresses one or more embryonic biomarkers. The reprogramming is accomplished by contacting the adult cells with a platelet rich fraction comprising platelet-like cells from umbilical cord blood or peripheral blood, and expanding the immature cell type in vitro under culture conditions to generate an insulin-producing cell population that expresses human beta-cell specific transcription factors and is functionally equivalent to human pancreatic beta-cells. Without being limited by theory, platelet-like cells and their released mitochondria display immune tolerance-associated markers that may modulate the function and differentiation of immune cells. The described invention further provides a pharmaceutical composition comprising a cell product containing a therapeutic amount of an insulin-producing cell population derived from functionally reprogrammed adult cells, wherein the ...

Compositions and methods for treating and diagnosing cancer

Isolation and use of solid tumor stem cells

P \OPER\HPM\Regnts of the Unirs y of Mchipn464M2I.div page.doc-MAI/2 8 A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the 5 majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumors in the mammary gland of severely immunodeficient mice. These xenograft assay 10 have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.

"ENERGETIC" CANCER STEM CELLS (E-CSCS): A NEW HYPER-METABOLIC AND PROLIFERATIVE TUMOR CELL PHENOTYPE, DRIVEN BY MITOCHONDRIAL ENERGY

This disclosure describes the characteristics of the ''energetic'' cancer stem cell (e-CSC) phenotype. This distinct sub-population of cancer stem cells (CSCs) has a unique energetic profile compared to bulk CSCs, being more glycolytic, having higher mitochondrial mass and elevated oxidative metabolism. e-CSCs also show an increased capacity to undergo cell cycle progression, enhanced anchorage-independent growth, and ALDH-positivity. The e-CSC phenotype presents new targets for cancer therapeutics, and in particular the anti-oxidant response, mitochondrial energy production, and mitochondrial biogenesis of e-CSCs makes them highly susceptible to mitochondrial inhibitors that target e-CSC anti-oxidant response, mitochondrial energy production, and mitochondrial biogenesis. Gene products for e-CSCs are disclosed, as well as classes of mitochondrial inhibiting therapeutic agents. Also disclosed are methods for identifying and separating e-CSCs from bulk cell populations.

METHODS AND COMPOSITIONS FOR CHARACTERIZATION OF GLIOBLASTOMA MULTIFORME TUMORS AND CANCER STEM CELLS

A method of characterizing a glioblastoma multiforme (GBM) stem cell (GSC), comprising culturing the GSC to provide a culture, contacting a first set of aliquots of the culture with individual compounds selected from a panel of compounds, identifying two or more of the selected compounds that cause more than a threshold level of cell death in the first set of aliquots, and characterizing the GSC as suitable for treatment with one or more combinations comprising the two or more identified compounds. A panel of anti-GBM chemotherapeutic compounds, the compounds selected by a method comprising surgically resecting the tumor, culturing a GSC derived from GBM tissue derived from a GBM tumor, contacting aliquots thereof with individual compounds selected from a panel of compounds, and identifying two or more of the selected compounds that cause more than a threshold level of cell death in the aliquots, thereby identifying the compounds.

INDUCED EXTENDED PLURIPOTENT STEM CELLS, METHODS OF MAKING AND USING

Factors for extending the ability of isolated pluripotent stem cells to generate extraembryonic lineages in vivo, following in vitro culture, herein, chemical extenders of pluripotency (CEP). Methods of extending the ability of a pluripotent cell to generate embryonic and extraembryonic lineages. The cell to be reprogrammed is contacted with effective amounts of the CEPs for a sufficient period of time to reprogram the cell into a chemically induced extended pluripotent cell (ciEPSC). ciEPSC are identified as an extended pluripotent cell based on properties including: (i) morphologically and (ii) functionally for example, based on their ability contribute to both TE and ICM, in vivo. The ciEPSCs can be cultured or induced to differentiate into cells of a desired type, and used in a number of applications, including but not limited to cell therapy and tissue engineering.

INDUCED EXTENDED PLURIPOTENT STEM CELLS, METHODS OF MAKING AND USING

Factors for extending the ability of isolated pluripotent stem cells to generate extraembryonic lineages in vivo, following in vitro culture, herein, chemical extenders of pluripotency (CEP). Methods of extending the ability of a pluripotent cell to generate embryonic and extraembryonic lineages. The cell to be reprogrammed is contacted with effective amounts of the CEPs for a sufficient period of time to reprogram the cell into a chemically induced extended pluripotent cell (ciEPSC). ciEPSC are identified as an extended pluripotent cell based on properties including: (i) morphologically and (ii) functionally for example, based on their ability contribute to both TE and ICM, in vivo. The ciEPSCs can be cultured or induced to differentiate into cells of a desired type, and used in a number of applications, including but not limited to cell therapy and tissue engineering.

MARKERS OF ACUTE MYELOID LEUKEMIA STEM CELLS

Markers of acute myeloid leukemia stem cells (AMLSC) are identified. The markers are differentially expressed in comparison with normal counterpart cells, and are useful as diagnostic and therapeutic targets.

HUMAN ORAL MUCOSA STEM CELL SECRETOME

The present invention provides secretome derived from human oral mucosa stem cells (hOMSC), and cell-free compositions comprising hOMSC-derived secretome. Methods for obtaining, manipulating and using hOMSC-derived secretome in therapy, cosmetics and tissue regeneration are also provided.

TUMOR-INITIATING CELLS AND METHODS OF USE

Provided herein are an isolated or enriched population of tumor initiating cells derived from normal cells, cells susceptible to neoplasia, or neoplastic cells. Methods of use of the cells for screening for anti-hyperproliferative agents, and use of the cells for animal models of hyperproliferative disorders including metastatic cancer, diagnostic methods, and therapeutic methods are provided.

HUMAN CANCER STEM CELLS

This invention discloses isolated populations of human cancer stem cells. Methods for characterizing, isolating and culturing human cancer stem cells are also disclosed. Uses for human cancer stem cells are provided.

INDIVIDUALIZED HIGH PURITY HEPATOCELLULAR CARCINOMA STEM CELLS, METHODS AND USE OF THE SAME

The disclosure provides cancer stem cells, for use in stimulating immune response against a cancer, such as hepatocellular carcinoma (HCC). Methods for preparing and purifying the cancer stem cells are provided.

PRODUCTION OF STABLE NON-POLYADENYLATED RNAS

The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a 3' terminal stabilizing triple helical structure. Related methods for expressing said RNAs in vivo and in vitro are also disclosed.

RAPID METHOD PRODUCTION HIGH PURITY CANCER STEM CELLS AND POPULATION OF HIGH PURITY CANCER STEM CELLS

The disclosure provides reagents, including cells, and related methods, useful for administering to subjects with a neoplastic disorder. The reagents and methods encompass cancer stem cells of enhanced purity. Neoplastic disorder encompasses melanoma, ovarian cancer, colorectal cancer, breast cancer, and lung cancer.

THE METHOD OF INHIBITION OF PROLIFERATION OF CANCER CELLS IN THE STEM AGING CELL POPULATION OF EHRLICH ADENOCARCINOMA

METHODS OF IDENTIFICATION, CLEANING AND ENRICHMENT OF THE UNRIPE OR TRUNK CELL- INITIATORS OF MALIGNANT INCREASE FROM THE TUMORS AND THEIR APPLICATION

METHODS OF DETERMINING THERAPY ON BASIS OF CHARACTERISTICS OF SEPARATE CELLS FROM CIRCULATING TUMOR CELLS (TsOK) AT METASTATIC DISEASE

Tumor in-vitro culture method and clinical chemotherapeutic drug screening method

Polypeptide and application thereof

Pharmacy applications of MTA1 and inhibitor thereof

The invention relates to pharmacy applications of MTA1 and an inhibitor thereof. Specifically, the behaviors of MTA1 about keeping stem cell dry and promoting tumor stem cells self-renewal are discovered, and MTA1 can be taken as a molecular target in a tumor treatment strategy by taking tumor stem cells as a target spot. MTA1 can be used to prepare preparations for keeping stem cell dry, and the inhibitor of MTA1 can be used to prepare medicaments for preventing and/or treating tumors.

POLYPEPTIDE PROBE FOR DETECTING CD133

The present invention relates to a polypeptide probe for detecting CD133 functioning as a neuroglioma stem cell marker. The use of the polypeptide probe of the present invention enables the effective detection of neuroglioma stem cells. To this end, the polypeptide probe includes: (a) a polypeptide backbone made of an amino acid sequence represented by general formula 1, HxGC(GK)yC; and (b) a plurality of monopeptide probes coupled to the backbone and made of a first sequence on the sequence list. COPYRIGHT KIPO 2016 (AA) C (cysteine) : Formation of a probe structure in a cyclic form through a disulfide bond (BB) Peptide^* : CD133 binding peptide sequence, K M P K E N P S S W L S GCGK (FITC) ...

métodos de tratamento do câncer residual mínimo

CANCER-ASSOCIATED FIBROBLASTS IN MAINTAINING STEMNESS OF CANCER STEM CELLS

An in vitro co-culture system comprising cancer-associated fibroblasts (CAFs) and cancer cells for producing and maintaining cancer stem cells and uses thereof for identifying agents capable of reducing cancer cell stemness. Also disclosed herein are a paracrine network through which CAFs facilitate production and/or maintenance of cancer stem cells and the use of components of such a paracrine network for prognosis purposes and for identifying cancer patients who are likely to respond to certain treatment.

CULTURE MEDIUM AND METHOD FOR ENRICHING AND MAINTAINING CANCER STEM CELLS (CSCS) USING SAID MEDIUM

The invention relates to a cell culture medium for isolating and/or enriching cancer stem cells (CSCs), produced by means of the method that essentially comprises the culturing of mesenchymal stem cells in a conventional serum-free medium, and the collection of the medium thus produced. The resulting conditioned medium can be filtered, frozen and/or concentrated. The invention also relates to a CSC-enriching method consisting in sowing, in the previous conditioned medium, a sample containing CSCs, and producing the cell population produced, and to this same method, with the additional characteristic that, before culturing the CSCs in the conditioned medium, the culture is treated with diluted trypsin, and the cells sensitive to trypsin, which have a higher percentage of CSCs, are isolated.

METHODS FOR ISOLATING AND USING PITUITARY ADENOMA STEM CELLS AND PITUITARY ADENOMA CELLS

The present invention describes pituitary adenoma stem cells, pituitary carcinoma stem cells, a method of obtaining the stem cells, and a method of using the stem cells. Uses of the pituitary stem cells include but are not limited to producing pituitary hormones and identifying drugs to treat pituitary disease conditions or pituitary-related disease conditions.

Generation of neural stem cells from undifferentiated human embryonic stem cells

The present invention relates to the generation of neural cells from undifferentiated human embryonic stem cells. In particular it relates to directing the differentiation of human ES cells into neural progenitors and neural cells and the production of functioning neural cells and/or neural cells of a specific type. The invention also includes the use of these cells for the treatment of neurological conditions such as Parkinson's disease.

Methods of treating pre-malignant ductal cancer with autophagy inhibitors

Described herein are progenitor cancer cells and cell lines isolated from human breast ductal carcinoma in situ (DCIS) lesions and the uses of these cells or cell lines in drug design, drug screening, and monitoring in vivo therapy. The DCIS malignant precursor cells or cell lines are epithelial in origin, are positive for markers of autophagy, show at least one genetic difference from normal cells of said fragment, form 3-D tube-like structures or ball aggregates, or are inhibited in formation of 3-D structures and migration by treatment with chloroquine. In one embodiment, there is a loss of heterozygosity (LOH) that is narrowly confined to a region of chromosome 6p (6p21.1-6p12.3) that contains the SUPT3H gene.

CULTURE METHOD FOR CAUSING DIFFERENTIATION OF PLURIPOTENT MAMMALIAN CELLS

Provided is a method that achieves control of embryoid body size and can induce differentiation in a state where the embryoid body size is controlled, by using a cell culture chamber having a plurality of microchambers formed therein. A culture method for causing differentiation of pluripotent mammalian cells uses a cell culture chamber (10) having a plurality of microchambers (11) formed on a culture surface. The cell culture chamber (10) has a culture surface formed of spaces in which the microchambers (11) have a space structure with a height of 10 μm to 500 μm and a bottom area of 100 μm2 to 1 mm2. The culture method for causing differentiation of pluripotent mammalian cells includes culturing pluripotent mammalian cells to obtain a cell population at least partially differentiated into endoderm lineage cells, by using the cell culture chambers (10).

HORMONE RESPONSIVE TISSUE CULTURE SYSTEM AND USES THEREOF

The invention provides tissue culture system for primary cells (e.g. normal mammalian primary epithelial progenitors). This system includes: a) a serum-free, chemically defined cell culture media; and, b) methods for isolation and in vitro long-term propagation of primary cells (e.g. primary epithelial cells). Primary cells so isolated and cultured can be kept undifferentiated and proliferate for many weeks (>15 weeks) or population doubling (>35 PD) without senescence, or any detectable genetic alterations. Upon changing media/culture conditions, these cells can be induced to differentiate. The invention also provides methods to transform normal primary cells so cultured into “cancer stem cells.” The genetically defined cancer stem cell tumor model mimics the behavior of the disease closely, e.g., the cells are invasive, hormone responsive and metastatic when injected into mice. The tumor cells express genes that are specific to cancer stem cells identified in patient samples.

Identification, Isolation and Elimination of Cancer Stem Cells

Isolated populations of leukemic stem cells are provided. The cells are useful for experimental evaluation, and as a source of lineage and cell specific products, and as targets for the discovery of factors or molecules that can affect them. Detection of leukemic stem cells is useful in predicting disease progression, relapse, and development of drug resistance. Proliferation of LSC may be inhibited through interfering with activation of the β-catenin pathway. Methods are provided for the clinical staging of pre-leukemia and leukemias by differential analysis of hematologic samples for the distribution of one or more hematopoietic stem or progenitor cell subsets.

METHOD TO INHIBIT CELL GROWTH USING OLIGONUCLEOTIDES

Described are methods for treating hyperproliferative disorders, including cancers, by administering to the affected mammal (e.g., human) an effective amount of a composition comprising one or more oligonucleotides which share at least 33% but less than 100% nucleotide sequence identity with the human telomere overhang repeat. Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, atopic dermatitis, or hyperproliferative diseases of other epithelia and methods for reducing photoaging, or oxidative stress or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are also disclosed. The compositions and methods are also useful for treating other cancers, such as for example pancreatic cancer and eradicating cancer stem cells.

COMPOSITIONS AND METHODS FOR TREATING AND DIAGNOSING CANCER

The present invention relates to compositions and methods for treating, characterizing, and diagnosing cancer. In particular, the present invention provides gene expression profiles and signatures associated with solid tumor stem cells, as well as novel stem cell cancer markers useful for the diagnosis, characterization, prognosis and treatment of solid tumor stem cells. More particularly, the present invention identifies two profiles of cancer stem cells useful for the diagnosis, characterization, and treatment of cancer and cancer metastases. The invention also provides a variety of reagents such as stem cell gene signatures for use in the diagnosis and management of cancer.

METHOD FOR MAINTAINING AND AMPLIFYING COLON CANCER STEM CELLS AND METHOD FOR INDUCING COLON CANCER ORGANOID

The present invention provides a method for maintenance and expansion of a colon cancer stem cell or induction of a colon cancer organoid. In addition, the present invention provides a medicament screening system using a colon cancer stem cell maintained and expanded or a colon cancer organoid induced by the method.

СПОСОБ ПОЛУЧЕНИЯ ПЛЮРИПОТЕНТНЫХ СТВОЛОВЫХ КЛЕТОК

Изобретение относится к области биотехнологии. Предложен способ получения плюрипотентных стволовых клеток, включающий процесс дедифференцировки соматических клеток, культивирование индуцированных плюрипотентных стволовых клеток в присутствии агента, изменяющего эпигенетический статус клетки, и культивирование стволовых клеток в отсутствие указанного агента. При этом процесс дедифференцировки соматических клеток проводят посредством их модификации с помощью факторов перепрограммирования в среде, содержащей ингибитор метилтрансферазы GSK126, а культивирование индуцированных плюрипотентных стволовых клеток в присутствии агента, изменяющего эпигенетический статус клетки, проводят в среде, содержащей белки Вах и Bak. Изобретение позволяет получать индуцированные плюрипотентные стволовые клетки, способные к полному дозреванию и способные дифференцироваться в клетки с низкой вероятностью развития их канцерогенеза, а также увеличение скорости получения плюрипотентных стволовых клеток и дифференцированных ...

Способ получения глиальных производных индуцированных плюрипотентных стволовых клеток с повышенной экспрессией NGF для терапии нейродегенеративных заболеваний

Изобретение относится к области биотехнологии, в частности к cпособу получения глиальных предшественников, полученных из индуцированных плюрипотентных стволовых клеток, с повышенной экспрессией NGF для терапии нейродегенеративных заболеваний. Изобретение обеспечивает получение клеточной культуры модифицированных глиальных предшественников, которая демонстрирует экспрессию глиального маркера s100β, стимулирует повышенную выживаемость мозжечковых нейронов и обладает выраженным антиамнестическим действием за счет повышенной секреции нейротрофина NGF. 2 ил., 3 табл., 3 пр.

Compositions and methods for treating and diagnosing cancer

Peripheral zone tumor cells, methods for their preparation and use

The present invention relates to a tumor cell of the peripheral zone of a tumor and methods of providing such a tumor cell. Further provided is a method for identifying a molecular marker diagnostic for an infiltrative cancer, an antibody, which specifically binds to such molecular marker, a method for identifying a therapeutic compound effective against a metastatic/infiltrative cancer disease and the use of a tumor cell according to the invention.

Cells, islets, and organoids that evade immune detection and autoimmunity, methods of production and use thereof

The invention features cells, islet-like cells, pancreatic islets and organoids (e.g., human islet-like organoids or HILOs), as well as cell cultures and methods that are useful for the rapid and reliable generation of cells and organoids, such as pancreatic islets and organoids, that are sustainable in vivo and that evade immune detection, rejection and autoimmunity. The invention also features methods of treating pancreatic diseases, such as type 2 diabetes, and pancreatic cancer, using the cells, islet-like cells, pancreatic islets and organoids (e.g., HILOs) that are designed to modulate the activity of immune cells that would otherwise react against them.

Adhesive signature-based methods for the isolation of cancer-associated cells and cells derived therefrom

The present invention provides methods of isolating a cancer-associated cell, such as a cancer stem cell or tumor initiating cell or a cell derived therefrom, from a mixture of cells, for example, a mixture of adherent cells in culture. Cell isolation is achieved by the application of selective detachment forces.

METHODS FOR PRODUCING CANCER STEM CELL SPHEROIDS

The invention provides a method for producing a population of ready-to-use spheroid forming cancer cells, comprising:(i) growing cancer cells in suspension culture in a first culture medium on one or more first low-adhesion tissue culture plates thereby forming cancer cell spheroids enriched in cancer stem cells; (ii) disaggregating said cancer cell spheroids to form a suspension of single cells enriched in cancer stem cells; (iii) plating said suspension of single cells in a second culture medium on one or more second low-adhesion tissue culture plates; and (iv) freezing said suspension of single cells in said one or more second tissue culture plates, thereby producing a population of ready-to-use spheroid forming cancer cells. Also provided are cell populations produced by the method and kits for growing cancer cell spheroids, including for use in screening of test compound.

METHODS OF DETERMINING THERAPIES BASED ON SINGLE CELL CHARACTERIZATION OF CIRCULATING TUMOR CELLS (CTCS) IN METASTATIC DISEASE

The disclosure provides a method of identifying a cell type, or the presence or absence of a cell type, associated with response to abiraterone or enzalutamide in a cancer patient, comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characterization of nucleated cells in a blood sample obtained from the patient to identify and enumerate circulating tumor cells (CTC); (b) isolating the CTCs from the sample; (c) individually characterizing parameters to generate a profile for each of the CTCs, and (d) identifying a biomarker CTC, wherein presence or absence of the biomarker CTC indicates a responsiveness in the patient to abiraterone or enzalutamide.

COMPOSITIONS AND METHODS FOR ORGANOID GENERATION AND DISEASE MODELING

The invention features pancreatic islet and pancreatic organoids, and cell cultures and methods that are useful for the rapid and reliable generation of pancreatic islet and pancreatic islet organoids. The invention also features methods of treating pancreatic diseases and methods of identifying agents that are useful for treatment of pancreatic diseases, such as type 2 diabetes and pancreatic cancer, using the pancreatic islet and pancreatic organoids of the invention.

COMPOSITIONS AND METHODS FOR REPROGRAMMING ADULT CELLS THROUGH THE STEMNESS OF A PLATELET RICH FRACTION OF BLOOD CONTAINING PLATELET-LIKE CELLS IN HUMANS

The described invention provides a method of functionally reprogramming adult cells to an immature cell type that expresses one or more embryonic biomarkers. The reprogramming is accomplished by contacting the adult cells with a platelet rich fraction comprising platelet-like cells from umbilical cord blood or peripheral blood, and expanding the immature cell type in vitro under culture conditions to generate an insulin-producing cell population that expresses human beta-cell specific transcription factors and is functionally equivalent to human pancreatic beta-cells. Without being limited by theory, platelet-like cells and their released mitochondria display immune tolerance-associated markers that may modulate the function and differentiation of immune cells. The described invention further provides a pharmaceutical composition comprising a cell product containing a therapeutic amount of an insulin-producing cell population derived from functionally reprogrammed adult cells, wherein the ...

IMPROVED BLOOD-BRAIN BARRIER ENDOTHELIAL CELLS DERIVED FROM PLURIPOTENT STEM CELLS FOR BLOOD-BRAIN BARRIER MODELS

The invention relates to a method of creating a human blood-brain barrier (BBB) model from the differentiation of human pluripotent stem cells (hPSCs), wherein the BBB exhibits sustained transendothelial electrical resistances (TEER) over 2000 O. cm2 for at least 3 days after seeding.