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.

Modified cells comprising a transmembrane polypeptide comprising at least one extracellular target receptor-binding domain, a transmembrane domain and an intracellular domain, wherein said intracellular domain is not capable of transducing any signal are provided. Methods of inducing or inhibiting signaling by a target receptor in a target cell comprising contacting the target cell with a modified cell of the invention 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 DYRK1A inhibitor and a GLP1R agonist. The disclosure further describes a method of regenerating pancreatic beta cells in a transplant patient.

An object of the present invention is to provide a method for producing insulin-producing cells having sufficient glucose responsiveness from mesenchymal stem cells, an insulin-producing cell having sufficient glucose responsiveness, a cell structure containing the insulin-producing cell, and a pharmaceutical composition. According to the present invention, there is provided a method for producing an insulin-producing cell from a mesenchymal stem cell, including (a) a step of producing a cell structure by incubating a plurality of biocompatible macromolecular blocks and a plurality of mesenchymal stem cells, and (b) a step of culturing one or more of the mesenchymal stem cells before the incubation in the step (a), the mesenchymal stem cell in the incubation in the step (a), or the cell structure produced in the step (a) in a medium containing the GLP-1 receptor agonist, and (c) a step of culturing the cell structure obtained in the step (a) or the step (b) in a medium containing the water-soluble vitamin and the hepatocyte growth factor.

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.

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.

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.

An object of the present invention is to provide a method for producing insulin-producing cells having sufficient glucose responsiveness from mesenchymal stem cells, an insulin-producing cell having sufficient glucose responsiveness, a cell structure containing the insulin-producing cell, and a pharmaceutical composition. According to the present invention, there is provided a method for producing an insulin-producing cell from a mesenchymal stem cell, including (a) a step of producing a cell structure by incubating a plurality of biocompatible macromolecular blocks and a plurality of mesenchymal stem cells, and (b) a step of culturing one or more of the mesenchymal stem cells before the incubation in the step (a), the mesenchymal stem cell in the incubation in the step (a), or the cell structure produced in the step (a) in a medium containing the GLP-1 receptor agonist, and (c) a step of culturing the cell structure obtained in the step (a) or the step (b) in a medium containing the water-soluble vitamin and the hepatocyte growth factor.

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.

Modified cells comprising a transmembrane polypeptide comprising at least one extracellular target receptor-binding domain, a transmembrane domain and an intracellular domain, wherein the intracellular domain is not capable of transducing any signal are provided. Methods of inducing or inhibiting signaling by a target receptor in a target cell comprising contacting the target cell with a modified cell of the invention are also provided.