Pancreatic stem cells and uses thereof

Abstract

The disclosure relates to stem cells and their therapeutic use in the treatment and/or prevention of pancreatic diseases or disorders. Provided herein are compositions comprising c-kit positive pancreatic stem cells and methods of preparing and using c-kit positive pancreatic stem cells for the treatment and/or prevention of pancreatic diseases or disorders.

What is claimed is: 
     
         1 . A method of treating or preventing a pancreatic disease or disorder in a subject in need thereof comprising administering isolated pancreatic stem cells to the subject wherein the pancreatic stem cells are isolated from a pancreatic tissue specimen and are c-kit positive. 
     
     
         2 . The method of  claim 1 , wherein the pancreatic stem cells are adult pancreatic stem cells. 
     
     
         3 . The method of  claim 1 , wherein the pancreatic stem cells are characterized by their ability to differentiate into endocrine cells and/or exocrine cells. 
     
     
         4 . The method of  claim 1 , wherein the pancreatic disease or disorder is diabetes. 
     
     
         5 . The method of  claim 1 , wherein said isolated pancreatic stem cells are expanded in culture prior to administration to the subject. 
     
     
         6 . The method of  claim 1 , wherein the isolated pancreatic stem cells are exposed to one or more cytokines and/or growth factors prior to administration to the subject. 
     
     
         7 . The method of  claim 1 , wherein the isolated pancreatic stem cells are exposed to Stem Cell Factor (SCF), insulin-like growth factor 1 (IGF-1), and/or hepatocyte growth factor (HGF) prior to administration to the subject. 
     
     
         8 . The method of  claim 1 , wherein the pancreatic tissue specimen is obtained from the subject. 
     
     
         9 . The method of  claim 1 , wherein the isolated pancreatic stem cells are administered to the subject by injection or by a catheter system. 
     
     
         10 . A method of isolating resident pancreatic stem cells from a pancreas comprising:
 (a) culturing a tissue specimen from said pancreas in culture, thereby forming a tissue explant;   (b) selecting cells from the cultured explant that are c-kit positive, and   (c) isolating said c-kit positive cells, wherein said isolated c-kit positive cells are resident pancreatic stem cells.   
     
     
         11 . The method of  claim 10 , wherein said isolated c-kit positive cells express one or more markers of exocrine and/or endocrine cells selected from insulin, C-peptide, glucagon, CK19 and amylase. 
     
     
         12 . The method of  claim 10 , wherein said isolated c-kit positive cells are capable of generating one or more pancreatic cell types selected from an exocrine cell, an endocrine cell, an alpha cell and a beta cell. 
     
     
         13 . The method of  claim 10 , further comprising expanding said isolated c-kit positive cells in culture. 
     
     
         14 . The method of  claim 10 , wherein said isolated c-kit positive cells are clonogenic, multipotent and self-renewing. 
     
     
         15 . The method of  claim 10 , further comprising exposing said isolated c-kit positive cells to one or more cytokines and/or growth factors in culture. 
     
     
         16 . The method of  claim 10 , further comprising exposing said isolated c-kit positive cells to Stem Cell Factor (SCF), IGF-1, and/or HGF in culture. 
     
     
         17 . A method of repairing and/or regenerating damaged tissue of a pancreas in a subject in need thereof comprising: extracting pancreatic stem cells from a pancreas; culturing and expanding said pancreatic stem cells, said pancreatic stem cells being c-kit positive stem cells; and administering a dose of said extracted and expanded pancreatic stem cells to an area of damaged tissue in the subject effective to repair and/or regenerate the damaged tissue of the pancreas. 
     
     
         18 . The method of  claim 17 , wherein the extracted and expanded c-kit positive stem cells express one or more markers of exocrine and/or endocrine cells selected from insulin, C-peptide, glucagon, CK19 and amylase. 
     
     
         19 . The method of  claim 17 , wherein the extracted and expanded c-kit positive stem cells are capable of generating one or more pancreatic cell types selected from an exocrine cell, an endocrine cell, an alpha cell and a beta cell. 
     
     
         20 . The method of  claim 17 , wherein the extracted and expanded c-kit positive stem cells are exposed to one or more cytokines and/or growth factors prior to administration to the damaged tissue. 
     
     
         21 . The method of  claim 17 , wherein the extracted and expanded c-kit positive stem cells are exposed to Stem Cell Factor (SCF), IGF-1, and/or HGF prior to administration to the damaged tissue. 
     
     
         22 . The method of  claim 17 , wherein the extracted and expanded c-kit positive stem cells are administered by catheter-mediated or direct injection.