Cell compositions derived from dedifferentiated reprogrammed cells

Abstract

Disclosed herein are cell culture compositions, for example, pancreatic cell culture compositions, derived from dedifferentiated human reprogrammed pluripotent stem cells, such as induced pluripotent stem (iPS) cells, and methods for producing and using such cell culture compositions.

1 - 7 . (canceled) 
     
     
         8 . A device comprising a semi-permeable membrane, and a pancreatic progenitor cell population derived from dedifferentiated genetically reprogrammed pluripotent mammalian stem cells, wherein the semi-permeable membrane encapsulates the pancreatic progenitor cell population. 
     
     
         9 . The device of  claim 8 , wherein the dedifferentiated genetically reprogrammed pluripotent mammalian stem cells are induced pluripotent stem cells. 
     
     
         10 . The device of  claim 8 , wherein the pancreatic progenitor cell population comprises endocrine cells and non-endocrine cells. 
     
     
         11 . The device of  claim 10 , wherein the endocrine cells are chromogranin positive (CHGA + ) cells. 
     
     
         12 . The device of  claim 10 , wherein the non-endocrine cells are chromogranin negative (CHGA − ) cells. 
     
     
         13 . The device of  claim 12 , wherein the CHGA −  cells express NKX6 transcription factor related locus 1 (NKX6.1). 
     
     
         14 . The device of  claim 10 , wherein at least 5% of the pancreatic progenitor cell population comprises non-endocrine cells. 
     
     
         15 . The device of  claim 8 , wherein the pancreatic progenitor cell population comprises pancreatic-duodenal homeobox factor-1 (PDX1) positive pancreatic endoderm cells. 
     
     
         16 . The device of  claim 8 , wherein the device comprises micro perforations. 
     
     
         17 . The device of  claim 8 , wherein the mammalian stem cells are human stem cells. 
     
     
         18 . The device of  claim 8 , wherein the device is biodegradable. 
     
     
         19 . The device of  claim 8 , wherein the pancreatic progenitor cell population is an aggregate suspension of pancreatic progenitor cells. 
     
     
         20 . A method for producing insulin in vivo comprising, transplanting endocrine and non-endocrine cell populations derived from dedifferentiated genetically reprogrammed pluripotent cells into a mammal and maturing the non-endocrine cell population into insulin secreting cells that secrete insulin in vivo in response to glucose stimulation. 
     
     
         21 . The method of  claim 20 , wherein the non-endocrine cell population is CHGA− cells. 
     
     
         22 . The method of  claim 20 , wherein the endocrine cell population is CHGA+ cells. 
     
     
         23 . The method of  claim 21 , wherein the CHGA− cells express NKX6.1. 
     
     
         24 . An in vitro method of producing human pancreatic progenitor cells comprising:
 a) obtaining a population of human cells comprising foregut endoderm cells; and   b) culturing the population of human cells comprising foregut endoderm cells in a medium comprising an ErbB receptor tyrosine kinase activating agent, thereby generating human pancreatic progenitor cells.   
     
     
         25 . The in vitro method of  claim 24 , wherein the ErbB receptor tyrosine kinase activating agent comprises an epidermal growth factor (EGF) family ligand. 
     
     
         26 . The in vitro method of  claim 25 , wherein the EGF family ligand is Heregulin-1 (Neuregulin-1), Heregulin-2 (Neuregulin-2), Heregulin-3 (Neuregulin-3) or Heregulin-4 (Neuregulin-4). 
     
     
         27 . The in vitro method of 26, wherein Heregulin-1 (Neuregulin-1) is heregulin-1 β.