Use of anti-aging glycopeptides to enhance pancreatic 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 .- 18 . (canceled) 
     
     
         19 . A method for enhancing engraftment of isolated pancreatic cells, isolated pancreatic progenitor cells, or both comprising the step of:
 a) contacting an isolated pancreatic cell, an isolated pancreatic progenitor cell, or both prior to a transplantation in a 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, and then washing the isolated pancreatic cell, the isolated pancreatic progenitor cell, or both to remove the compound:   
       
         
           
           
               
               
           
         
       
     
     
         20 . The method of  claim 19 , further comprising:
 b) transplanting the treated isolated pancreatic cell of step a) in said subject in need thereof.   
     
     
         21 . The method of  claim 20 , further comprising step a′) before step a):
 a′) isolating pancreatic cells, pancreatic progenitor cells, or both. 
 
     
     
         22 . The method of  claim 20 , further comprising step b′) before step b) contacting the isolated pancreatic cell, the isolated pancreatic progenitor cells, or both of step a) with an immunosuppressant drug. 
     
     
         23 . The method of  claim 19 , wherein said isolated pancreatic cell is an isolated alpha cell, an isolated beta cell, an isolated delta cell, an isolated gamma cell, an epsilon cell, or a combination thereof. 
     
     
         24 . The method of  claim 19 , wherein said isolated pancreatic cell is an isolated beta cell. 
     
     
         25 . The method of  claim 22 , wherein said immunosuppressant drug is one of daclizumab, sirolimus, tacrolimus, cyclosporine, or combinations thereof. 
     
     
         26 . The method of  claim 19 , wherein said subject is a human subject. 
     
     
         27 . The method of  claim 19 , wherein said isolated pancreatic cell is isolated from a live donor, a cadaveric donor, or combinations thereof. 
     
     
         28 . The method of  claim 19 , wherein the isolated pancreatic cell, the isolated pancreatic progenitor cell, or both are contacted with the compound for an hour. 
     
     
         29 . The method of  claim 19 , wherein concentration of said compound is from about 1 mg/ml to about 5 mg/ml. 
     
     
         30 . The method of  claim 29 , 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. 
     
     
         31 . An isolated pancreatic cell, an isolated pancreatic progenitor cell, or both prepared according to the method of  claim 19 . 
     
     
         32 . A method of transplanting isolated pancreatic cells, isolated pancreatic progenitor cells, or both in a subject in need thereof comprising the steps of:
 a) transplanting an isolated pancreatic cell, an isolated pancreatic progenitor cell, or both prepared according to the method of  claim 19 , in said subject in need thereof.   
     
     
         33 . The method of  claim 19 , further comprising the step of:
 b) transplanting the isolated pancreatic cell, the treated isolated pancreatic progenitor cell, or both from step a) in said subject in need thereof, wherein said subject is receiving an immunosuppressant drug.   
     
     
         34 . The method of  claim 33 , wherein the immunosuppressant drug is daclizumab, sirolimus, tacrolimus, cyclosporine, or a combination thereof.