Disclosed are methods for conditionally immortalizing stem cells, including adult and embryonic stem cells, the cells produced by such methods, therapeutic and laboratory or research methods of using such cells, and methods to identify compounds related to cell differentiation and development or to treat diseases, using such cells. A mouse model of acute myeloid leukemia (AML) and cells and methods related to such mouse model are also described.

The present invention provides a method for producing a retinal pigment epithelial cell, including (1) a first step of subjecting pluripotent stem cells to floating culture in a serum-free medium to form an aggregate of pluripotent stem cells, (2) a second step of subjecting the aggregate formed in step (1) to floating culture in a serum-free medium or serum-containing medium each being free of a substance acting on the Sonic hedgehog signal transduction pathway and containing a substance acting on the BMP signal transduction pathway, thereby obtaining an aggregate containing retinal progenitor cells, and (3) a third step of subjecting the aggregate formed in step (2) to floating culture in a serum-free medium or serum-containing medium each being free of a substance acting on the Sonic hedgehog signal transduction pathway and a substance acting on the BMP signal transduction pathway and containing a substance acting on the Wnt signal pathway, thereby obtaining an aggregate containing retinal pigment epithelial cell.

Embodiments disclosed here provide engineered modified hematopoietic stem cells (HSCs), artificially prostaglandin E2 (PGE.sub.2)-stimulated HSCs, compositions comprising these HSCs, methods of using these modified HSCs for treating autoimmune diseases and disorders and for suppressing the immune system. In particular, the engineered modified HSCs or PGE.sub.2-stimulated HSCs express the surface marker, programmed cell death-1 ligand 1 (PD-L1).

The invention is directed to methods for culturing cells so that the cells are induced to differentiate into cells that express a hepatic stellate phenotype. The invention is also directed to cells produced by the methods of the invention. The cells are useful, among other applications, for treatment of liver deficiencies, liver metabolism studies, and liver toxicity studies, fibrogenic studies, or to support hepatocyte function in co-culture setting.

Methods using a soft polysaccharide hydrogel for an organoid culture are described. An example method includes preparing a cell suspension in a cell culture medium. The cells of the cell suspension embedded or cultured in the 3D cell culture biomatrix are injectable for in vivo application. The method also includes mixing a hydrogel solution with the cell suspension to form a soft hydrogel mixture, adding additional cell culture medium to the soft hydrogel mixture to obtain cell colonies after a first time period, harvesting the cell colonies, mixing the hydrogel solution with the cell colonies to create a 3D cell culture biomatrix, adding cell differential medium to the hydrogel solution, replacing the cell differential medium with an organoid transfer medium after a second time period, and replacing the organoid transfer medium with an organoid medium after a third time period.

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.

Provided is a manufacturing method for a plurality of regenerated hair follicle germs, including a step including simultaneously inoculating a microwell plate including regularly arranged microwell portions with mesenchymal cells and epithelial cells, and co-culturing the mesenchymal cells and the epithelial cells using a medium containing a fibroblast growth factor while supplying oxygen to the mesenchymal cells and the epithelial cells from at least an upper surface and a bottom surface of the microwell plate, to thereby form hair follicle germs in the microwell portions, the microwell plate being formed of a material having oxygen permeability. Also provided is a kit for hair regeneration, including: a microwell plate including regularly arranged microwell portions; and a fibroblast growth factor, wherein the microwell plate is formed of a material having oxygen permeability.

Methods of preparing naive human pluripotent stem cells are described. The methods include the use of xeno-free media and do not include the use of feeder cells.

Embodiments disclosed here provide engineered modified hematopoietic stem cells (HSCs), artificially prostaglandin E2 (PGE.sub.2)-stimulated HSCs, compositions comprising these HSCs, methods of using these modified HSCs for treating autoimmune diseases and disorders and for suppressing the immune system. In particular, the engineered modified HSCs or PGE.sub.2-stimulated HSCs express the surface marker, programmed cell death-1 ligand 1 (PD-L1).

Embodiments disclosed here provide engineered modified hematopoietic stem cells (HSCs), artificially prostaglandin E2 (PGE.sub.2)-stimulated HSCs, compositions comprising these HSCs, methods of using these modified HSCs for treating autoimmune diseases and disorders and for suppressing the immune system. In particular, the engineered modified HSCs or PGE.sub.2-stimulated HSCs express the surface marker, programmed cell death-1 ligand 1 (PD-L1).