The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

The present invention relates to hepatic organoids and uses thereof. The compositions include models for the study of developmental biology of the liver and other epithelial tissues, drug discovery and toxicity screening, infectious disease biology of various infectious agents, and personalized medicines. Methods for seeding canine intestinal organoids, maintaining an organoid monolayer, and monitoring monolayer integrity are provided. Methods and systems for culturing, freezing, and recovering the frozen organoid cells are also provided. The hepatic organoids may also be used to treat a subject in need, or for identifying a preferred therapeutic agent.

Compositions and methods are described herein for transdifferentiation of multipotent stromal cells into cells that can express insulin.

Compositions and methods are described herein for transdifferentiation of multipotent stromal cells into cells that can express insulin.

The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

Provided is a new type serum-free medium. The medium comprises: DMEM with high glucose (the content of glucose being 4.5 g/L), B27, recombinant human basic fibrolast growth factor (b-FGF), nicotinamide, N-2, vinblastine III (conophylline), non-essential amino acid (NEAA), heparin, epidermal growth factor (EGF), hepatocyte growth factor (HGF), a serum replacement (SR), an insulin-transferrin-selenium complex (ITS), and pentagastrin. Inducing differentiation of mesenchymal stem cells into insulin-secretion-like cells can be achieved in six days in one step using the medium.

Described herein are methods for providing an in vitro intestinal model system, e.g., using primary cells instead of cell lines and/or cancerous cells.

Disclosed are methods for making a vascularized hollow organ derived from human intestinal organoid (HIOs). The HIOs may be obtained from human embryonic stem cells (ESC's) and/or induced pluripotent stem cells (iPSCs), such that the HIO forms mature intestinal tissue. Also disclosed are methods for making a human intestinal tissue containing a functional enteric nervous system (ENS).

The present invention provides a cell culture medium for culturing primary gastrointestinal stromal tumor cells, comprising gastrin, N2, insulin, a receptor tyrosine kinase ligand, and a Rock kinase inhibitor. The present invention further provides a method for culturing gastrointestinal stromal tumor cells by using the cell culture medium, and an application and a method of an expanded cell population, which is obtained by using the method, in efficacy evaluation or screening.