Disclosed herein are cell cultures and enriched cell populations of endocrine precursor cells, immature pancreatic hormone-expressing cells and mature pancreatic hormone-expressing cells. Also disclosed herein are methods of producing such cell cultures and cell populations.

The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides an improved method for the formation of pancreatic endoderm, pancreatic hormone expressing cells and pancreatic hormone secreting cells. The present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer.

Methods, kits, compositions, and systems are provided for culturing pluripotent stem cells to produce populations of cells comprising beta-like cells (e.g., pancreatic lineage, glucose-responsive, and/or insulin-producing). In particular, culture conditions are provided that result in the generation of beta-like cells from a starting culture of human pluripotent stem cells.

The present disclosure relates to a pharmaceutical composition for prevention or treatment of non-alcoholic steatohepatitis, the composition comprising, as an active ingredient, exosomes isolated from induced pluripotent stem cell-derived mesenchymal stem cells which have been or have not been treated with a pretreatment material. The exosomes of the present disclosure exhibit a more improved effect of preventing or treating non-alcoholic steatohepatitis, compared to those isolated from conventional mesenchymal stem cells and as such, can be advantageously used for relevant research and development, and productization.

It is a main object of the present invention to provide a process for producing an insulin-producing cell from a somatic cell without performing artificial gene transfer, an insulin-producing cell obtained from the process, or a composition comprising a combination of chemical substances that can be used for the process. The present invention can include, for example: a process for producing an insulin-producing cell from a somatic cell by direct differentiation induction, comprising a step of culturing a somatic cell in the presence of an RSK inhibitor; an insulin-producing cell obtained from the process; and a composition for producing an insulin-producing cell from a somatic cell by directly inducing differentiation, comprising an RSK inhibitor. The insulin-producing cells obtained according to the present invention are useful in regenerative medicine and the like.

The present disclosure relates to a composition for promoting the production of stem cell-derived exosomes or increasing the stemness of stem cells. When the composition of the present disclosure is used in culturing stem cells, the stemness of stem cells and the yield of stem cell-derived exosomes are increased, and thus good-quality stem cells and stem cell-derived exosomes can be produced more efficiently, and accordingly, can be advantageously used in related research and development and commercialization.

Liver metabolism studies are limited by the inability to expand primary hepatocytes in vitro while maintaining their metabolic functions. Human hepatic three dimensional organoids have been established for use in these studies, but hepatic organoids from adult donors had impaired expansion. Methods of achieving expansion of adult donor-derived hepatic organoids (HepAOs) and HepG2 cells (HepGOs) from single cells in organoid cultures using combinations of growth factors and small molecules are described, with assessment of expansion dynamics, gluconeogenic and HNF4α expression, and albumin secretion. The invention discloses conditions including limiting A8301 and incorporating FSK and OSM to allow the expansion of HepAOs from adult donors and HepGOs with gluconeogenic competence. These models increase the repertoire of human hepatic cellular tools available for use in liver metabolic assays.

Disclosed herein are cell cultures and enriched cell populations of endocrine precursor cells, immature pancreatic hormone-expressing cells and mature pancreatic hormone-expressing cells. Also disclosed herein are methods of producing such cell cultures and cell populations.

It is a main object of the present invention to provide a new producing method capable of efficiently performing direct conversion or induction from a somatic cell to an insulin-producing cell. The present invention can include, for example, a process for producing an insulin-producing cell by direct differentiation induction from a somatic cell, comprising a step of culturing a somatic cell in a serum-free differentiation induction medium, or a step of culturing a somatic cell in a differentiation induction medium containing 5 μg/mL or more of insulin. According to the present invention, insulin-producing cells having a high insulin secretion ability can be produced directly and efficiently from a somatic cell. The insulin-producing cells obtained according to the present invention are useful in regenerative medicine and the like.

A population of enteroendocrine cells (EEC) is obtained from a mammalian post-natal cell population, such as a population including post-natal stem cells, by treating the population with a plurality of small molecules that upregulate ChgA and promote differentiation of the cells to form the enteroendocrine cells. The upregulation of ChgA is such that the fraction of cells expressing CGA in the obtained cell population, as measured by a ChgA Immunostaining Assay, is at least about 1.5%. Small molecules that can be used to differentiate the post-natal cells into the enteroendocrine cells can include at least one of a Wnt activator, a Notch inhibitor, a Wnt inhibitor, a MEK/ERK inhibitor, a growth factor, a HDAC inhibitor, a Histone Methylation Inhibitor, a Tgf-β inhibitor, and a NeuroD1 activator. Also, the insulin expression of a population of mammalian cells is increased by treating the population with a plurality of small molecules that increase the insulin expression.