Drug Screening Using Islet Cells and Islet Cell Progenitors 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 factor chosen from a drug, a solvent, a peptide and a polynucleotide for its effect on a primate pancreatic islet cell precursor expressing Sox 17 comprising
 a) contacting a cell culture of primate pancreatic islet cells precursors expressing Sox 17 with a factor;   b) observing a change in the primate pancreatic islet cell precursor expressing Sox 17 after a); and   c) correlating the change in the primate pancreatic islet cell precursor expressing Sox 17 with the factor.   
     
     
         2 . The method of claim, one wherein the pancreatic islet cell precursors expressing Sox 17 are human cells. 
     
     
         3 . The method of claim one, wherein the primate pancreatic islet cell precursor expressing Sox 17 are the in vitro progeny of a primate pluripotent stem cell. 
     
     
         4 . The method of claim one, wherein the factor is a drug. 
     
     
         5 . The method of claim one, wherein the factor is a solvent. 
     
     
         6 . The method of claim one, wherein the factor is a peptide. 
     
     
         7 . The method of claim one, wherein the factor is a polynucleotide. 
     
     
         8 . The method of claim one, wherein the primate pancreatic islet cell precursor expressing Sox 17 also expresses HNF3β. 
     
     
         9 . The method of  claim 1 , wherein observing a change in the primate pancreatic islet cell precursor expressing Sox 17 comprises observing a morphological change in the primate pancreatic islet cell precursor expressing Sox 17. 
     
     
         10 . The method of  claim 1 , wherein observing a change in the primate pancreatic islet cell precursor expressing Sox 17 comprises observing a phenotypic change in the primate pancreatic islet cell precursor expressing Sox 17. 
     
     
         11 . A method of screening a factor chosen from a drug, a solvent, a peptide and a polynucleotide for its effect on a primate pancreatic islet cell or islet cell precursor expressing insulin, comprising
 a) contacting a cell culture of primate pancreatic islet cells or islet cell precursors expressing insulin with a factor;   b) observing a change in the primate pancreatic islet cell or islet cell precursor expressing insulin after a); and   c) correlating the change in the primate pancreatic islet cell or islet cell precursor expressing insulin with the factor;   wherein the pancreatic islet cell or islet cell precursor is the in vitro progeny of a primate pluripotent stem cell.   
     
     
         12 . The method of  claim 11 , wherein the primate pancreatic islet cell or islet cell precursors are human cells. 
     
     
         13 . The method of  claim 11  comprising determining if the factor's affects insulin expression or insulin secretion. 
     
     
         14 . The method of  claim 11  comprising determining if the compound affects growth of primate pancreatic islet cells or pancreatic islet cell precursors. 
     
     
         15 . The method of  claim 11 , wherein the factor is a drug. 
     
     
         16 . The method of  claim 11 , wherein the factor is a solvent. 
     
     
         17 . The method of  claim 11 , wherein the factor is a peptide. 
     
     
         18 . The method of  claim 11 , wherein the factor is a polynucleotide.