Methods of Inducing Regulated Pancreatic Hormone Production in Non-Pancreatic Islet Tissues

Abstract

Disclosed are methods and pharmaceutical compositions for inducing pancreatic hormone production.

1 . A method of inducing or enhancing a pancreatic islet cell phenotype or function in a population of non-pancreatic cells, said method comprising contacting said cell population with a composition comprising a PDX polypeptide thereby increasing PDX polypeptide expression in the cell population, in an amount sufficient to induce or enhance pancreatic islet cell phenotype or function in said cell population. 
     
     
         2 . The method of  claim 1 , wherein said PDX is ectopic or endogenous. 
     
     
         3 . The method of  claim 1 , wherein said cell is a pluripotent stem cell 
     
     
         4 . The method of  claim 1 , wherein said cell is a hepatic stem cell. 
     
     
         5 . The method of  claim 1 , wherein said cell population comprises a muscle cell, a spleen cell, a kidney cell, a blood cell, a skin cell, a pancreas cell or a liver cell. 
     
     
         6 . The method of  claim 1 , wherein said cell population is provided in vitro. 
     
     
         7 . The method of  claim 1 , wherein said cell population is provided ex vivo from a mammalian subject. 
     
     
         8 . The method of  claim 1 , wherein said cell population is provided in vivo. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein said inducing or enhancing pancreatic islet cell phenotype or function comprises inducing or enhancing at least two pancreatic islet cell characteristics selected from the group consisting of an islet gene expression profile, production of a pancreatic hormone, processing of a pancreatic hormone, storage of a pancreatic hormone and secretion of a pancreatic hormone. 
     
     
         17 . The method of  claim 16 , wherein said pancreatic hormone is insulin, somatostatin, or glucagon. 
     
     
         18 . The method of  claim 16 , wherein said islet cell gene expression profile comprises increased expression of PC1/3, insulin, glucagon or somatostatin. 
     
     
         19 . A method of inducing or enhancing a pancreatic islet cell phenotype or function in a population of non-pancreatic cells, said method comprising contacting said cell population with a composition comprising a PDX polypeptide in an amount sufficient to induce or enhance pancreatic islet cell phenotype or function in said cell population by increasing PDX expression in said cell population, such that the cell population exhibits at least two characteristics of pancreatic islet cells. 
     
     
         20 . The method of  claim 22 , wherein said PDX is ectopic or endogenous. 
     
     
         21 . The method of  claim 22 , wherein said characteristics of pancreatic islet cells is selected from the group consisting of an islet gene expression profile, production of a pancreatic hormone, processing of a pancreatic hormone, storage of a pancreatic hormone and secretion of a pancreatic hormone. 
     
     
         22 . The method of  claim 21 , wherein said pancreatic hormone is insulin, somatostatin, or glucagon. 
     
     
         23 . The method of  claim 21 , wherein said islet gene expression profile comprises increased expression of PC1/3, insulin, glucagon or somatostatin.