Method for Transdifferentiation of Non Pancreatic Stem Cells to the Pancreatic Differentiation Pathway

Abstract

The subject invention comprises culture methods for transdifferentiation of non-pancreatic stem cells to the pancreatic differentiation pathway. It also concerns the endocrine hormones that can be produced by such cultures, and the use of the transdifferentiated cells in the treatment of pancreatic diseases.

1 . A transdifferentiated mesenchymal stem cell (MSC) produced by the method comprising the step of 
 culturing mesenchymal stem cells in a medium that permits the expression of pancreatic differentiation markers.    
   
   
       2 . The transdifferentiated MSC of  claim 1  wherein said medium comprises Dulbecco's Minimal Essential Medium (DMEM) with high glucose and sodium pyruvate, bovine serum albumin (BSA), 2-mercaptoethanol, fetal calf serum (FCS), penicillin and streptomycin (Pen-Strep), and insulin, transferrin and selenium (ITS) for at least about 10-14 days.  
   
   
       3 . The transdifferentiated MSC of  claim 1  wherein the pancreatic markers that are expressed are selected from the group consisting of Isl-1, Pax-6, Glut-2, glucagon and optionally PDX-1 or Pax4.  
   
   
       4 . The transdifferentiated MSC of  claim 1 , wherein the medium further contains an effective combination and effective concentration of growth factors selected from the group consisting of stem cell factor (SCF), glucagon-like peptide-1 (GLP-1), activin A, betacellulin, hepatocyte growth factor (HGF), epidermal growth factor (EGF), keratinocyte growth factor (KGF), prolactin (PRL), nerve growth factor (NGF), transforming growth factor-α (TGF-α), gastrin, and conditioned medium of a cell line selected from the group consisting of Capan-1, ARIP and AR42J.  
   
   
       5 . The transdifferentiated MSC of  claim 4  wherein the growth factors comprise SCF, GLP-1, activin A, betacellulin, HGF, EGF, KGF, PRL, NGF, TGF-α, gastrin and conditioned medium of a cell line selected from the group consisting of Capan-1, ARIP and AR42J.  
   
   
       6 . The transdifferentiated MSC of  claim 6  wherein the mesenchymal stem cells are CD105+, CD166+, CD29+ and CD44+.  
   
   
       7 . The transdifferentiated MSC of  claim 1  wherein the mesenchymal stem cells are human.  
   
   
       8 . A transdifferentiated MSC that expresses mRNA for Isl-1, Pax-6, Glut-2, glucagon and optionally Pdx-1 or Pax4.  
   
   
       9 . A therapeutic composition comprising a transdifferentiated MSC encapsulated in an endocrine hormone permeable capsule.