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 system for generating insulin expressing cells comprising a) a first in vitro population of cells comprising human embryonic stem cells; and b) a second isolated cell population comprising progeny of a portion of the first population of cells, wherein the progeny express insulin c-peptide. 
   
   
       2 . The system of  claim 1 , wherein the first and second populations of cells are contained in separate containers. 
   
   
       3 . The system of  claim 1 , wherein the second population of cells is contained in a device comprising a semi-permeable membrane. 
   
   
       4 . The system of  claim 1 , wherein the first population of cells is genetically modified. 
   
   
       5 . The system of  claim 1 , wherein the second population of cells is genetically modified. 
   
   
       6 . A system for generating gut endoderm cells comprising a) a first in vitro population of cells comprising human embryonic stem cells; and b) a second cell population comprising progeny of a portion of the first population of cells, wherein the progeny express Sox17, HNF1a and HNF3P. 
   
   
       7 . The system of  claim 6 , wherein the first and second populations of cells are contained in separate containers. 
   
   
       8 . The system of  claim 6 , wherein the first population of cells is genetically modified. 
   
   
       9 . The system of  claim 6 , wherein the second population of cells is genetically modified. 
   
   
       10 . A system for generating insulin expressing cells comprising a) a first in vitro population of cells which express stage specific embryonic antigen 3 (SSEA3), stage specific embryonic antigen 4 (SSEA4), and markers detectable using antibodies designated Tra-1-60 and Tra-1-81; and b) a second isolated cell population comprising progeny of a portion of the first population of cells, wherein the progeny express insulin c-peptide. 
   
   
       11 . A system for generating gut endoderm cells comprising a) a first in vitro population of cells which express stage specific embryonic antigen 3 (SSEA3), stage specific embryonic antigen 4 (SSEA4) and markers detectable using antibodies designated Tra-1-60 and Tra-1-81; and b) a second cell population comprising progeny of a portion of the first population of cells, wherein the progeny express Sox17, HNF1α and HNF3p.