37results about "Cell differentiation" patented technology

The invention belongs to the technical field of biomedicine, and relates to a method for increasing the yield of pancreas islet organs differentiated by pluripotent stem cells and improving the stability. The method comprises the following steps: (1) inoculating pluripotent stem cells, and culturing by adopting a basic culture medium containing Y-27632; (2) changing the liquid, and continuously culturing by adopting a basic culture medium; (3) culturing for 1 day by using an S1D1 culture medium, and then culturing for 2-3 days by using an S1D2 culture medium; (4) changing the liquid, and culturing for 2-3 days by adopting the S2 culture medium; (5) changing the liquid, and culturing for 1-2 days by adopting an S3 culture medium; (6) changing the liquid, and culturing for 4-7 days by adopting a culture medium S4; (7) changing the liquid, and culturing for 3-10 days by adopting an S5 culture medium; and (8) carrying out cell sphere repolymerization, and culturing for 3-21 days by using an S6 culture medium to obtain the pancreas islet organ. The present invention increases the yield and differentiation efficiency at each differentiation stage and increases the scale yield at the cellular level.

The present invention relates to a method for generating an enriched population of early cortical neural stem cells (NSCs) or a subpopulation thereof, the method comprising: isolating cells that are positive for the cell surface marker protogenin (PRTG) from an initial population of neural progenitor cells, wherein said isolating is conducted at a time point between about day 4 and about day 12, preferably on day 5, after initiation of neural induction, thereby obtaining an enriched population of early cortical neural stem cells (NSCs); and optionally re- culturing said enriched population of early cortical neural stem cells (NSCs) in a neural induction medium or other culture medium, wherein said re-culturing preferably produces progeny of said early cortical neural stem cells (NSCs).

To provide methods of lineage specific differentiation of pluripotent stem cells, including induced pluripotent stem cells, into floor plate midbrain progenitor cells, determined dopamine (DA) neuron progenitor cells, and / or DA neurons.SOLUTION: Provided is a method of differentiating neural cells, the method comprising: (a) performing a first incubation comprising culturing pluripotent stem cells in a non-adherent culture vessel under conditions to produce a cellular spheroid; and (b) performing a second incubation comprising culturing cells of the spheroid in a substrate-coated culture vessel under conditions to neurally differentiate the cells.SELECTED DRAWING: Figure 1

The present invention relates to a natural killer (NK) cell that has been differentiated in vitro, as well as corresponding methods, compositions, kits, and therapeutic uses.

The present application provides a mutant basic-helix-loop-helix (bHLH) transcription factor that comprises a mutation of one or more phosphoacceptor site for proline-directed serine-threonine kinases alone or together with a mutation in a conserved PKA site in the HLH domain, found in the corresponding wild-type bHLH transcription factor, and exhibits reduced phosphorylation by proline-directed serine-threonine kinases and PKA. Also provided are nucleic acids encoding the mutant bHLH transcription factor, and vectors comprising the encoding nucleic acids. Use of the mutant bHLH transcription factor or nucleic acid encoding the mutant bHLH transcription factor for therapeutic purposes can efficiently induce neuronal lineage conversion of glial cells, even in an inhibitory environment, and are useful in preventing or treating neurodegenerative diseases and disorders, and for treating CNS injuries. Further provided a use a ZBTB 18 transcription factor or a nucleic acid encoding the ZBTB 18 transcription factor for neuronal lineage conversion of glial cells.

The present disclosure relates to compositions, constructs, and vectors for reprogramming cells into plasmacytoid dendritic cells or type I interferon-producing cells, as well as methods and uses thereof. The present disclosure relates to the development of methods for generating plasmacytoid dendritic cells or type I interferon-producing cells that promote antiviral and antitumor immune responses from differentiated cells, pluripotent stem cells, or pluripotent stem cells by introducing and expressing isolated / synthetic transcription factors. More specifically, the present disclosure unexpectedly provides methods for obtaining plasmacytoid dendritic cells or type I interferon-producing cells by direct cell reprogramming using specific combinations of transcription factors.

The disclosure features methods and compositions for differentiating stem cells into hematopoietic stem and progenitor cells (HSPC) and / or Natural Killer (NK) cells. The methods and compositions described herein are used to differentiate stem or progenitor cells having at least one gene-edit that is maintained in the differentiated cell. Also provided are differentiated cells produced using the methods and compositions described herein for therapeutic applications.

The present invention relates to a method for producing an in vitro model of a human neurological disease. Furthermore, the invention relates to the in vitro model produced according to the method disclosed herein. The invention also relates to the use of the in vitro model in drug testing. In addition, the invention relates to methods for testing the efficacy of drugs in preventing, delaying, and alleviating a human neurological disease.

The invention relates to a bioreactor cell culture system comprising a closed chamber containing a plurality of suspended cell microcompartments, wherein the microcompartments each comprise an outer hydrogel layer providing a cavity containing a set of self-organized cells and extracellular matrix or an extracellular matrix substitute. The invention further relates to the use of such bioreactors in methods for producing cells and / or organoids, and / or molecules and / or complex molecular assemblies.

Described in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and / or allogenic HSCs, using mechanical stretching or Trpv4 agonists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and / or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.

A method is provided for generating human forebrain neural progenitor cells and mature forebrain neurons from human pluripotent stem cells using a chemically defined medium. The method allows for the initial generation of OTX2+ FEZF2+ SIX3+ forebrain neural stem cells, which can then be cultured to generate NKX2-1+ ventral forebrain neural stem cells and subsequently ASCL1+ medial ganglia primitive neural progenitor cells (MGE-NPCs). The MGE-NPCs are further differentiated into immature neurons and mature GABAergic interneurons. Culture media, isolated cell populations, and kits are also provided.

The present invention relates to a Crystalline Form A of a compound of Chemical Formula 1 having physically and chemically outstanding characteristics compared to amorphous forms and other crystalline forms of the compound of Chemical Formula 1. Crystalline Form A of the compound of Chemical Formula 1 according to the present invention, compared to amorphous forms or other crystalline forms, does not denature even at prolonged exposure to harsh conditions, has low water sorption, is advantageous for formulation as the crystalline form does not change even under pressure or when pulverized, and the crystalline form itself has excellent stability, being useful for storage for extended periods.

To provide methods of lineage specific differentiation of pluripotent stem cells, including induced pluripotent stem cells, into floor plate midbrain progenitor cells, determined dopamine (DA) neuron progenitor cells, and / or DA neurons.SOLUTION: Provided is a method of differentiating neural cells, the method comprising: (a) performing a first incubation comprising culturing pluripotent stem cells in a non-adherent culture vessel under conditions to produce a cellular spheroid; and (b) performing a second incubation comprising culturing cells of the spheroid in a substrate-coated culture vessel under conditions to neurally differentiate the cells.SELECTED DRAWING: Figure 1

The present disclosure relates to compositions and methods for the conversion of source cells (such as cochlear support cells) to cochlea hair cells and / or cochlea hair cell-like cells by introducing transcription factors (TFs) into the source cells, and methods for treating hearing loss.

Disclosed is a method for producing a large amount of natural killer cells and the use of the natural killer cells as an anticancer agent. The method produces fresh NK cells with high purity within a short time, and can also produce cold-preserved NK cells and thawed cryopreserved NK cells having efficacy comparable to the fresh NK cells. NK cells having efficacy comparable to the fresh NK cells can also be produced from cryopreserved CD3-negative cells. The fresh NK cells, cold-preserved NK cells and cryopreserved NK cells exhibit therapeutic effects against various cancers, including colorectal cancer, lung cancer, liver cancer, pancreatic cancer and leukemia, indicating these NK cells are effective as cellular therapeutic agents. Also disclosed are doses and methods of administration that show excellent effects when the fresh NK cells, cold-preserved NK cells and cryopreserved NK cells are used as pharmaceutical compositions for cellular therapy.

A first aspect of the invention relates to a method for preparing a three dimensional blood vessel organoid. In a second aspect, the invention is directed to three dimensional human blood vessel organoids obtained or obtainable from the method of the first aspect of the invention. A third aspect of the invention is related to the three dimensional human blood vessel organoids for use in (in vitro) drug screening and / or (in vitro) drug testing; and / or for use in (in vitro) toxicity analysis; and / or for use in (in vitro) bioengineering; and / or for (in vitro) transplant preparation.

Methods for generating induced trophoblast stem cells (iTSCs) from human cells are provided. Thus, methods are provided that include expressing exogenous GATA3 and OCT4 transcription factors in human cells under conditions that allow for the generation of iTSCs from the cells. Methods for rejuvenating and / or dedifferentiating human cells are also provided. Nucleic acid constructs, protein formulations, isolated human cells, human iTSCs, rejuvenated cells, and dedifferentiated cells are also provided.

Provided are: a method for culturing animal cells, wherein animal cells are cultured in the presence of an iron ion carrier such as hinokitiol; and a technique related thereto.

The present disclosure provides methods of lineage specific differentiation of pluripotent stem cells, including induced pluripotent stem cells, into floor plate midbrain progenitor cells, determined dopamine (DA) neuron progenitor cells, and / or DA neurons. Also provided are compositions and uses thereof, such as for treating neurodegenerative diseases and conditions, including Parkinson's disease.

The present invention relates to a method for isolating and culturing chicken primordial germline stem cells (PGCs) and constructing genetically modified chickens. Under an optimized culture system, short-term in vitro culture can yield millions of cells and establish stable lines. These lines can also be cultured for over 200 days in vitro while maintaining migration capacity. After genetic modification of the PGCs established in vitro, genetically modified chickens can be obtained via vascular injection. Furthermore, PGCs injected into the blood vessels of chicken embryos can be sorted on the seventh day of incubation, recultured in vitro, and then injected back into the blood vessels of the chicken embryo, thereby improving the efficiency of constructing genetically modified chickens. The present invention also involves freezing PGCs, achieving a resuscitation survival rate exceeding 80%, allowing for long-term storage of isolated or genetically modified PGCs. The present invention has the advantages of high isolation and culture efficiency, and the two-vascular injection method can improve the efficiency of constructing genetically modified chickens. The present invention has promising application prospects in the in vitro isolation, culture, line establishment, cryopreservation, and construction of genetically modified chickens from chicken PGCs.

Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic islet cells. In some aspects, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof. In some aspects, the disclosure provides for novel assays for assessing β cell potency.

Provided is a method for efficiently manufacturing high-purity peripheral nerve cells from undifferentiated cells. The method for manufacturing peripheral nerve cells from undifferentiated cells having an ability to differentiate into peripheral nerve cells includes the following steps (a) and (b): (a) culturing undifferentiated cells having an ability to differentiate into peripheral nerve cells to induce differentiation into neural progenitor cells without detaching a grown colony from a culture vessel; and (b) detaching the neural progenitor cells produced in the step (a) from the culture vessel, then seeding the cells at a seeding density of 2×105 to 6×105 cells / cm2 to a culture vessel, and culturing the cells for 14 to 42 days.

Methods, compositions and cells are provided that identify and isolate a population of adult non-embryonic progenitor cells having multilineage potential, physical diameters of about 2 μm to about 8 μm in size or about 4 μm to about 6 μm, and expressing at least one of the stem cell associated genes among Oct-4, KLF-4, Nanog, Sox-2, Rex-1, GDF-3 or Stella. Methods are also provided that identify and isolate populations, which are subsets or subpopulations of progenitor adult stem cells within the population of the adult stem cells which is a heterogeneous population, the methods including contacting the adult stem cells with a ligand specific for at least one of: CD99, tetraspan, ICAM4, full-length MUC1, and truncated MUC1 receptor, in which a presence of a surface protein on the cells that bind to the ligand identifies the population which is the subset of the differentiated progenitor adult stem cells.

The invention relates to a combination of small molecule reprogramming agents for inducing the generation of totipotent stem cells, a method for preparing the induced totipotent stem cells and the induced totipotent stem cells generated therefrom.

The invention relates to a combination of small molecule reprogramming agents for inducing the generation of totipotent stem cells, a method for preparing the induced totipotent stem cells and the induced totipotent stem cells generated therefrom.

The present invention relates to a method for providing a cell population enriched for neurons and / or their precursors, comprising obtaining a cell population comprising neuronal precursors and selecting positive cells, which indicate whether the cells have a high propensity to develop into neurons.

The bioink disclosed herein includes one or more cells, a carrier material, and microspheres. The microspheres can include one or more biodegradable polymers and one or more compounds, such as a morphogenic compound. The methods disclosed herein can include three-dimensional bioprinting. Additional methods disclosed herein include producing functional tissue.

The present invention provides methods for producing mature hepatocytes by increasing the expression of at least one transcription factor selected from the group consisting of nuclear factor IX (NFIX) and nuclear factor IC (NFIC) in immature hepatocytes, and compositions thereof.