The present invention relates to a method, which patterns 3D organoids prepared from human pluripotent stem cells and chops the same so as to culture oligodendrocyte progenitor cells, and induces the differentiation thereof so as to obtain a large quantity of finally differentiated oligodendrocytes. Compared to cells differentiated by a conventional differentiation method, oligodendrocytes obtained in a large quantity have the same or superior reproducibility, stability, and functionality and have remarkably shortened differentiation time, and thus are expected to be very useful for cell therapeutic agents or for screening for therapeutic drugs.

Methods for generating human committed midbrain neural stem cells (NSCs) and midbrain neural progenitor cells (midbrain NPCs) from human pluripotent stem cells are provided using chemically-defined culture media that allow for generation of the midbrain NPCs in as little as six days. The midbrain NPCs can be further differentiated to mature dopaminergic neurons. Culture media, isolated cell populations and kits are also provided.

A method of obtaining a pluripotent-like multipotent cell, including providing a cell of a first type which is not a pluripotent-like multipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pluripotent gene regulator in the cell of a first type, to a level at which the at least one pluripotent gene regulator is capable of driving transformation of the cell of a first type into the pluripotent-like multipotent cell; and placing or maintaining the cell in a differentiation medium and maintaining intracellular levels of the at least one pluripotent gene regulator for a sufficient period of time to allow a stable pluripotent-like multipotent cell to be obtained; wherein the pluripotent-like multipotent cell so obtained does not exhibit teratoma formation in vivo.

The present invention relates generally to the field of cell biology of stem cells, more specifically the directed differentiation of pluripotent or multipotent stem cells, including human embryonic stem cells (hESC), somatic stem cells, and induced human pluripotent stem cells (hiPSC) using novel culture conditions. Specifically, methods are provided for obtaining neural tissue, floor plate cells, and placode including induction of neural plate development in hESCs for obtaining midbrain dopamine (DA) neurons, motor neurons, and sensory neurons. Further, neural plate tissue obtained using methods of the present inventions are contemplated for use in co-cultures with other tissues as inducers for shifting differentiation pathways, i.e. patterning.

Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

Among the various aspects of the present disclosure is the provision of methods and compositions for the generation of functionally mature beta cells having enhanced SIX2+ activity and therapeutic benefit and uses thereof. An aspect of the present disclosure provides for a method of generating SIX2-enhanced SC-β cells. In some embodiments, the method comprises providing a population of SC-β cells (or EP cells); providing a SIX2 positive regulator; and/or incubating the population of SC-β cells and the SIX2 positive regulator.

Disclosed herein are compositions and methods to decellularize an isolated organ or portion thereof. Also disclosed herein are compositions and methods for treatment of disease utilizing a decellularized or recellularized organ. Also disclosed herein are methods of improving decellularization and/or recellularization of an isolated organ or portion thereof.

The present invention relates to a differentiation method for obtaining a large quantity of microglia by patterning, proliferating, culturing, and inducing the differentiation of yolk sac-mimic 3D organoids prepared from human pluripotent stem cells, wherein the microglia thus obtained in a large quantity exhibit significantly superior effects in terms of yield, purity, and storage stability compared to cells differentiated by existing differentiation methods, and thus may be utilized in research on lesions and therapeutic mechanisms of brain diseases, and drug screening platforms.

Methods for generating in culture of cells resembling mammalian trophectoderm-lineage cells from mammalian pluripotent stem cells are provided, along with the related compositions.