Methods for differentiating human pluripotent stem cells to dorsal neuroectoderm progenitors and further to glial progenitor cells and oligodendrocyte progenitor cells (OPCs) using inhibitors of BMP signaling and MAPK/ERK signaling are provided. Also provided are cells and cellular compositions obtained by such methods, and uses of such cells. Further provided are methods and protocols for efficiently differentiating human pluripotent stem cells to OPCs in the absence of the ventralizing morphogen SHH or a SHH signaling activator. The methods of the present disclosure reproducibly produce dorsal neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor.

Disclosed herein are compositions and methods related to megakaryocyte-derived extracellular vesicles derived from human pluripotent stem cells, where the megakaryocyte-derived extracellular vesicles may be utilized for drug delivery and treating various diseases.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Disclosed herein are methods for producing red blood cells (RBCs) from a population of stem cells and/or progenitor cells. In at least one of the stem cells or progenitor cells, SH2B3 protein activity is decreased, SH2B3 mRNA level is decreased, and/or SH2B3 protein level is decreased. The methods provided herein permit the production of RBCs with increased quantity and/or quality as compared to a method using the same population of stem cells and/or progenitor cells without SH2B3 inhibition or disruption. Also provided herein are methods of use of the RBCs produced using the methods described herein.

A trait induction method of undifferentiated cells is provided, including: culturing undifferentiated cells on abase material which has an uneven pattern on the surface to which the cells adhere and of which the width of the unevenness is 1 nm to 1,000 nm.

The present disclosure provides compositions and methods for the treatment or prophylaxis of a perfusion disorder, such as ischemia and/or reperfusion injury, in a subject's organ, tissue or extremity by preserving or improving endothelial function, reducing vascular injury, and/or promoting vascular repair. The disclosed compositions comprise endothelial colony-forming cells or a serum-free composition comprising chemically defined media conditioned by endothelial colony-forming cells.

The present disclosure provides methods for generating megakaryocytes and novel platelet variants from the same CD34+ progenitor stem cells, which comprises at least two stages: stage zero (0) comprising an expansion and maintenance stage of the CD34+ progenitor stem cells for a period ranging between 0 hours to 48 hours; and, stage one (I) comprising a differentiation phase wherein the differentiation phase comprises differentiating the CD34+ progenitor stem cells in step (i) for a period sufficient to generate substantially matured megakaryocytes. Novel platelet variants are produced by passaging the megakaryocytes, produced by the CD34+ progenitor stem cells, through a bioreactor or a fluidic device. Formulations comprising megakaryocytes and platelet variants derived from CD34+ progenitor stem cells and methods of their use are also disclosed.

The present disclosure provides multicellular culture models for the study of neuroinflammation, such as to identify novel targets, biomarkers, and therapeutic agents for the diagnosis, prognosis, and treatment of neurodegenerative diseases. Further provided herein are assays for studying neuroinflammation using the present cell culture models.

The present disclosure relates generally to methods and compositions useful in cell and tissue biology and therapeutics. In particular, an in vitro method for differentiating pluripotent stem cells into KDR.sup.+NCAM.sup.+APLNR.sup.+ mesoderm cells and/or SSEA5.sup.−KDR.sup.+NCAM.sup.+APLNR.sup.+ mesoderm cells is provided. The disclosed mesoderm cells may be used to generate blood vessels in vivo and/or further differentiated in vitro into endothelial colony forming cell-like cells (ECFC-like cells). Purified human cell populations of KDR.sup.+NCAM.sup.+APLNR.sup.+ mesoderm cells and ECFC-like cells are provided. Test agent screening and therapeutic methods for using the cell populations of the present disclosure are provided.