Use of anti-aging glycopeptides to enhance beta cell health, survival and improve transplant outcome

Abstract

The present disclosure relates to an in vitro method for enhancing engraftment of isolated pancreatic cells comprising the step of contacting an isolated pancreatic cell prior to a transplantation in a subject in need thereof, with a gem-difluorinated C-glycopeptide compound of general formula I, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate of the compound of general formula I:

1 . A method for enhancing engraftment of isolated human pancreatic cells, isolated human pancreatic progenitor cells, or both comprising the step of:
 a) contacting an isolated human pancreatic cell, an isolated human pancreatic progenitor cell, or both prior to a transplantation in a human subject in need thereof, with a gem-difluorinated C-glycopeptide compound of formula III, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate thereof:   
       
         
           
           
               
               
           
         
       
     
     
         2 . The method of  claim 1 , further comprising:
 b) transplanting the treated isolated human pancreatic cell of step a) in said human subject in need thereof.   
     
     
         3 . The method of  claim 2 , further comprising step a′) before step a):
 a′) isolating human pancreatic cells, human pancreatic progenitor cells, or both. 
 
     
     
         4 . The method of  claim 2 , further comprising step b′) before step b) contacting the isolated human pancreatic cell, the isolated human pancreatic progenitor cells, or both of step a) with an immunosuppressant drug. 
     
     
         5 . The method of  claim 1 , wherein said isolated human pancreatic cell is an isolated human alpha cell, an isolated human beta cell, an isolated human delta cell, an isolated human gamma cell, an isolated human epsilon cell, or a combination thereof. 
     
     
         6 . The method of  claim 1 , wherein said isolated human pancreatic cell is an isolated human beta cell. 
     
     
         7 . The method of  claim 4 , wherein said immunosuppressant drug is one of daclizumab, sirolimus, tacrolimus, cyclosporine, or combinations thereof. 
     
     
         8 . The method of  claim 1 , wherein said isolated human pancreatic cell is isolated from a live human donor, a cadaveric human donor, or combinations thereof. 
     
     
         9 . The method of  claim 1 , wherein the isolated human pancreatic cell, the isolated human pancreatic progenitor cell, or both are contacted with the compound for an hour. 
     
     
         10 . The method of  claim 1 , wherein concentration of said compound is from about 1 mg/ml to about 5 mg/ml. 
     
     
         11 . The method of  claim 10 , wherein concentration of said compound in step a) is from about 1 mg/ml to about 3 mg/ml, or from about 3 mg/ml to about 5 mg/ml. 
     
     
         12 . An isolated human pancreatic cell, an isolated human pancreatic progenitor cell, or both prepared according to the method of  claim 1 . 
     
     
         13 . A method of transplanting isolated human pancreatic cells, isolated human pancreatic progenitor cells, or both in a human subject in need thereof comprising the steps of:
 a) transplanting an isolated human pancreatic cell, an isolated human pancreatic progenitor cell, or both prepared according to the method of  claim 1 , in said human subject in need thereof.   
     
     
         14 . The method of  claim 1 , further comprising the step of:
 b) transplanting the isolated human pancreatic cell, the treated isolated human pancreatic progenitor cell, or both from step a) in said human subject in need thereof, wherein said subject is receiving an immunosuppressant drug.   
     
     
         15 . The method of  claim 14 , wherein the immunosuppressant drug is daclizumab, sirolimus, tacrolimus, cyclosporine, or a combination thereof.