The present invention belongs to the field of biomedicine, and relates to an inducer for inducing a mesenchymal stem cell to differentiate into an islet cell. An inducer for inducing a mesenchymal stem cell to differentiate into an islet cell consisted of the following components: GLP-1, parathyroid hormone, paracetamol, rapamycin, icariin, trametinib, EPO and VEGF. Each component in a inducer for inducing a mesenchymal stem cell to differentiate into an islet cell of the present invention is safe and non-toxic, requiring fewer steps and short time to induce differentiation, with high induction efficiency.

Provided herein are, inter alia, methods, compositions, and kits for culturing and improving the quality of islet cells. Included are compositions and kits for the ex vivo culture of islets or islet cells as well as methods of making and using the same. Isolated and cultured islets and islet cells are also provided.

Disclosed herein are methods of increasing cell proliferation in a population of pancreatic beta cells. Also disclosed are methods of treating a subject for a condition associated with insufficient insulin secretion. Also disclosed is a composition comprising a DYRK1 A inhibitor and a GLP1R agonist. The disclosure further describes a method of regenerating pancreatic beta cells in a transplant patient.

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

The present invention provides methods to promote the differentiation of pluripotent stem cells and the products related to or resulting from such methods. In particular, the present invention provides an improved method for the formation of pancreatic hormone expressing cells and pancreatic hormone secreting cells. In addition, the present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer and the products related to or resulting from such methods. The present invention also provides methods to promote glucose-stimulated insulin secretion in insulin-producing cells derived from pluripotent stem cells.

The invention provides novel compounds, in particular peptide and peptide analogs, which exhibit functionalities useful for treating a variety of diseases and conditions, particularly diseases and conditions relating to diabetes. The compounds of the invention are also useful for treating impaired pancreatic function, treating metabolic diseases, ex vivo islet induction, expansion and proliferation for transplantation, increasing the survival of transplanted islets in vivo, promoting neuroprotection or nerve regeneration, promoting liver regeneration, and inhibiting inflammation.

It is an object of the present invention to provide a method for preparing or separating pancreatic progenitor cells (or a group of pancreatic progenitor cells) that do not contain undifferentiated cells and efficiently differentiate into pancreatic islet cells. More specifically, the present invention relates to: pancreatic progenitor cells that appear in the process of differentiation of stem cells into pancreatic islet cells, which are characterized in that the pancreatic progenitor cells are positive to CD82; an agent for treating blood glucose level impairment, wherein the agent comprises the pancreatic progenitor cells; and a method for preparing pancreatic progenitor cells, wherein the method comprises separating CD82-positive cells.

Disclosed herein are methods, systems, and compositions for enhancing the effectiveness of β-cell (Beta-cell)-based therapies. Also disclosed herein are methods, systems, and compositions related to identifying, sorting and separating heterogeneous populations of stem cell-derived pancreatic β-cells (sBCs) into more useful and functionally homogeneous cell populations. In many embodiments, the most mature and functional of the sBCs are identified and live-sorted using the cell surface protein Ectonucleoside Triphosphate Diphosphohydrolase-3 (ENTP3), which is also referred to as CD39L3. The presently disclosed methods, systems, and compositions are useful for cell therapies, for example replacement therapy. In many embodiments the disclosed systems, methods, and compositions are useful in treatments for diabetes. In some embodiments, the disclosed methods, systems, and compositions may be useful in treating, preventing, and/or curing diabetes, for example type-1 diabetes.

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.

The invention provides novel compounds, in particular peptide and peptide analogs, which exhibit functionalities useful for treating a variety of diseases and conditions, particularly diseases and conditions relating to diabetes. The compounds of the invention are also useful for treating impaired pancreatic function, treating metabolic diseases, ex vivo islet induction, expansion and proliferation for transplantation, increasing the survival of transplanted islets in vivo, promoting neuroprotection or nerve regeneration, promoting liver regeneration, and inhibiting inflammation.