Methods for generating cardiomyocytes

Abstract

The present disclosure provides method of generating cardiomyocytes from post-natal fibroblasts. The present disclosure further provides cells and compositions for use in generating cardiomyocytes.

1 . A method of generating an induced cardiomyocyte, the method comprising: introducing into a human post-natal fibroblast reprogramming factors comprising Gata4, Mef2c, Tbx5, Mesp1, and Esrrg, wherein said introducing results in direct reprogramming of the post-natal fibroblast into a cardiomyocyte, thereby generating an induced cardiomyocyte. 
     
     
         2 - 10 . (canceled) 
     
     
         11 . A genetically modified post-natal fibroblast, wherein the genetically modified post-natal fibroblast is a human post-natal fibroblast that is genetically modified with one or more exogenous nucleic acids comprising nucleotide sequences encoding reprogramming factors comprising Gata4, Mef2c, Tbx5, Mesp1, and Esrrg. 
     
     
         12 . The genetically modified post-natal fibroblast of  claim 11 , wherein the one or more exogenous nucleic acids is integrated into the genome of the fibroblast. 
     
     
         13 . A composition comprising the genetically modified post-natal fibroblast of  claim 11 . 
     
     
         14 - 15 . (canceled) 
     
     
         16 . An induced cardiomyocyte derived from the genetically modified post-natal fibroblast of  claim 12 . 
     
     
         17 . An induced cardiomyocyte generated using the method of  claim 1 . 
     
     
         18 . A composition comprising the induced cardiomyocyte of  claim 16 . 
     
     
         19 - 20 . (canceled) 
     
     
         21 . A reprogramming composition comprising:
 a) one of:
 i) reprogramming factors comprising Gata4, Mef2c, Tbx5, Mesp1, and Esrrg polypeptides; or 
 ii) one or more nucleic acids comprising nucleotide sequences encoding reprogramming factors comprising Gata4, Mef2c, Tbx5, Mesp1, and Esrrg; and 
   b) a buffer.   
     
     
         22 . The reprogramming composition of  claim 21 , further comprising a pharmaceutically acceptable excipient. 
     
     
         23 . The reprogramming composition of  claim 21 , further comprising a therapeutic agent or thymosin 4. 
     
     
         24 . An implantable device comprising the reprogramming composition of  claim 21 . 
     
     
         25 . The implantable device of  claim 24 , wherein the device is a stent. 
     
     
         26 . The implantable device of  claim 24 , wherein the reprogramming composition is a controlled-release composition. 
     
     
         27 . A method of generating an induced cardiomyocyte in vivo, the method comprising:
 administering to an individual in need thereof an effective amount of the reprogramming composition of  claim 21 , wherein the reprogramming factors induce the human cardiac fibroblast to become a cardiomyocyte.   
     
     
         28 - 31 . (canceled) 
     
     
         32 . A method for performing cell transplantation in a recipient individual in need thereof, the method comprising: (i) generating an induced cardiomyocyte from a post-natal fibroblast of a human donor individual, wherein the donor individual is immunocompatible with the recipient individual, and wherein said induced cardiomyocyte is generated according to the method of  claim 1 ; and (ii) transplanting the induced cardiomyocyte into the recipient individual. 
     
     
         33 . The method of  claim 32 , wherein said recipient and said donor are the same individual. 
     
     
         34 . The method of  claim 32 , wherein said recipient and said donor are different individuals.