Method for in vitro preconditioning of myoblasts before transplantation

Abstract

Methods of pretreating healthy donor's myoblast cultures with growth or trophic factors on transplantation into subjects suffering from myopathic conditions such as muscular dystrophy. Compositions comprising myoblasts and fusion-promoting metalloproteases can be transplanted. Alternatively, myoblasts can be transplanted along with an agent inducing the expression of a fusion-promoting metalloprotease, or a composition comprising genetically-modified myoblasts capable of expressing a fusion-promoting metalloprotease can be transplanted.

1 . A method for increasing the number of transplanted myoblasts which migrate into a recipient muscle tissue and which fuse either with the myoblasts or muscle fibers of said recipient muscle tissue, said method comprising transplanting into a patient affected by a recessive myopathy a composition comprising myoblasts transformed with a gene construct capable of expressing a metalloprotease involved in extracellular matrix destruction.  
   
   
       2 . The method of  claim 1 , wherein the metalloprotease is Gelatinase A, Matrilysine, or both.  
   
   
       3 . The method of  claim 1 , wherein the expression of said metalloprotease is inducible.  
   
   
       4 . The method of  claim 1 , wherein said myoblasts to be transplanted are grown in vitro in a culture medium, suitable for growth of myoblasts, which comprises a growth or trophic factor.  
   
   
       5 . The method of  claim 4 , wherein said growth or trophic factor is basic fibroblast growth factor.  
   
   
       6 . The method of  claim 1 , wherein the recessive myopathy affecting said patient is Duchenne muscular dystrophy.