Method of isolating bile duct progenitor cells

Abstract

The present invention relates to a substantially pure population of viable bile duct progenitor cells, and methods for isolating such cells. The present invention further concerns certain therapeutic uses for such progenitor cells, and their progeny.

1 . (canceled)  
     
     
         2 . A cellular composition comprising, as the cellular component, a substantially pure population of viable pancreatic progenitor cells, which progenitor cells are capable of proliferation in a culture medium and differentiate to pancreatic lineages.  
     
     
         3 . The composition of  claim 2 , wherein at least 80% of the viable cells in the composition are progenitor cells.  
     
     
         4 . The composition of  claim 2 , which progenitor cells are from a mammal.  
     
     
         5 . The composition of  claim 4 , which mammal is a transgenic mammal.  
     
     
         6 . The composition of  claim 4 , which mammal is a primate.  
     
     
         7 . The composition of  claim 6 , which mammal is a human.  
     
     
         8 . The composition of  claim 4 , which mammal is a miniature swine.  
     
     
         9 - 13 . (canceled)  
     
     
         14 . The composition of  claim 2 , wherein the progenitor cells express one or more of STF-1; a PAX gene; PTF-1; hXBP-1; an HNF gene; villin; tyrosine hydroxylase; insulin; glucagon; or neuropeptide Y.  
     
     
         15 . The composition of  claim 14 , wherein the progenitor cells express STF-1 and PAX6.  
     
     
         16 - 19 . (canceled)  
     
     
         20 . The composition of  claim 2 , which progenitor cells can be maintained in culture for at least about 7 days.  
     
     
         21 . (canceled)  
     
     
         22 . A cellular composition consisting essentially of, as the cellular population, viable pancreatic progenitor cells capable of self-regeneration in a culture medium, which progenitor cells differentiate to members of the pancreatic lineage.  
     
     
         23 . The composition of  claim 22 , which progenitor cells are isolated from a hepatic duct tissue, or are the progeny thereof.  
     
     
         24 . The composition of  claim 22 , which progenitor cells are isolated from cystic duct tissue, or are the progeny thereof.  
     
     
         25 . The composition of  claim 22 , which progenitor cells are isolated from pancreatic duct tissue, or are the progeny thereof.  
     
     
         26 . The composition of  claim 22 , which progenitor cells are isolated from common bile duct tissue, or are the progeny thereof.  
     
     
         27 . The composition of  claim 22 , which progenitor cells are responsive to one or more growth factor selected from a group consisting of IGF, EGF, TGF, FGF, HGF and VEGF, or orthologous or paralogous factors thereof.  
     
     
         28 . A cellular composition comprising pancreatic progenitor cells, wherein the progenitor cells are at least 80% pure, are capable of self-regeneration in a culture medium and differentiate to pancreatic lineages.  
     
     
         29 . The composition of  claim 28 , which progenitor cells are inducible to differentiate into pancreatic islet cells.  
     
     
         30 . The composition of  claim 29 , which islet cells are pancreatic β islet cells.  
     
     
         31 . The composition of  claim 29 , which islet cells are pancreatic α islet cells.  
     
     
         32 . The composition of  claim 29 , which islet cells are pancreatic δ islet cells.  
     
     
         33 . The composition of  claim 29 , which islet cells are pancreatic φ islet cells.  
     
     
         34 . The composition of  claim 28 , wherein the progenitor cells are characterized by expression of STF-1 and PAX6.  
     
     
         37 . A pharmaceutical composition comprising the cellular composition of  claim 2 .  
     
     
         39 . A pharmaceutical composition comprising the cellular composition of  claim 22 .  
     
     
         40 . A pharmaceutical composition comprising the cellular composition of  claim 28 .  
     
     
         41 - 54 . (canceled)  
     
     
         55 . A method for treating a disorder characterized by insufficient insulin activity, in a subject, comprising introducing into the subject a pharmaceutical composition including a substantially pure population of pancreatic progenitor cells and a pharmaceutically acceptable carrier.  
     
     
         56 . The method of  claim 55 , wherein the subject is a human.  
     
     
         57 . The method of  claim 55 , wherein the disorder is an insulin dependent diabetes.  
     
     
         58 . The method of  claim 57 , wherein the insulin dependent diabetes is type I diabetes.  
     
     
         59 . The method of  claim 55 , wherein the pancreatic progenitor cells are induced to differentiate into pancreatic islet cells in the subject.  
     
     
         60 . The method of  claim 55 , wherein the pancreatic progenitor cells are induced to differentiate into pancreatic β islet cells in culture prior to introduction into the subject.  
     
     
         61 . The method of  claim 55 , wherein the pancreatic progenitor cells are characterized by expression of STF-1 and PAX6.  
     
     
         62 . A method for treating a disorder characterized by insufficient liver function, in a subject, comprising introducing into the subject a pharmaceutical composition including hepatic progenitor cells and a pharmaceutically acceptable carrier.  
     
     
         63 . The method of  claim 62 , wherein the subject is a human.  
     
     
         64 . The method of  claim 62 , wherein the disorder is selected from the group consisting of cirrhosis, hepatitis B, hepatitis C, sepsis or ELAD.  
     
     
         65 . The method of  claim 62 , wherein the hepatic progenitor cells are induced to differentiate into hepatocytes in the subject.  
     
     
         66 . The method of  claim 62 , wherein the hepatic progenitor cells are induced to differentiate into hepatocytes in culture prior to introduction into the subject.  
     
     
         67 . The method of  claim 62 , wherein the hepatic progenitor cells express HNF3, alphafetoprotein (AFP), albumin, and ATBF-1, and differentiate into hepatocytes.