Islet Cells from Human Embryonic Stem Cells

Abstract

This disclosure provides a system for producing pancreatic islet cells from embryonic stem cells. Differentiation is initiated towards endoderm cells, and focused using reagents that promote emergence of islet precursors and mature insulin-secreting cells. High quality populations of islet cells can be produced in commercial quantities for use in research, drug screening, or regenerative medicine.

1 . A method of screening a compound for its effect on a primate pancreatic islet cell or a pancreatic islet cell precursor comprising
 a) isolating a population of primate pancreatic islet cells or pancreatic islet cell precursors from a cell culture comprising primate pluripotent stem cells (pPS);   b) contacting the isolated population of primate pancreatic islet cells or pancreatic islet cell precursors with the compound; and   c) determining any affect from the compound to the isolated population of primate pancreatic islet cells or pancreatic islet cell precursors from b).   
     
     
         2 . The method of claim one wherein the primate pancreatic islet cells or pancreatic islet cell precursors are human cells. 
     
     
         3 . The method of claim one comprising determining if the compound is toxic to the primate pancreatic islet cells or pancreatic islet cell precursors. 
     
     
         4 . The method of claim one comprising determining if the compound affects insulin expression or insulin secretion. 
     
     
         5 . The method of claim one comprising determining if the compound affects growth of primate pancreatic islet cells or pancreatic islet cell precursors. 
     
     
         6 . A cell culture comprising a) a first population of cells comprising primate pluripotent stem cells (pPS); b) a second population of cells comprising cells that express Sox17, HNF3 and HNF4; and c) Activin A at a concentration suitable to induce expression of Sox17, HNF3 and HNF4 at level that is higher in the second population of cells compared to the first population of cells. 
     
     
         7 . The cell culture of  claim 6 , wherein the primate pluripotent stem cells (pPS) are human cells. 
     
     
         8 . The cell culture of  claim 6 , further comprising butyrate. 
     
     
         9 . The cell culture of  claim 6 , wherein the second population of cells comprises gut endodermal cells.