Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice

Cell Transplantation

Article

Joel Rousseau¹  Annick Michaud¹  Jacques P. Tremblay¹  Basma F. Benabdallah¹  Manaf Bouchentouf¹  Pascal Bigey²  Daniel Scherman²  Pierre Chapdelaine³ 

[1] Génétique humaine, Centre de Recherche du CHUL, Québec, Canada;Inserm, U640, CNRS, UMR8151, René Descartes Paris 5 University, Faculté des Sciences Pharmaceutiques et Biologiques, Chemical and Genetic Pharmacology Laboratory, Ecole Nationale Suprieure de Chimie de Paris, Paris, France;Ontogénie et reproduction, Centre de Recherche du CHUL, Québec, Canada;

关键词: Duchenne muscular dystrophy;    Myoblast transplantation;    Myostatin;    Follistatin;   

DOI  :  10.3727/096368908784153913

 received in 2007-06-11, accepted in 2007-07-16,  发布年份 2008

来源: Sage Journals

【 摘 要 】

Duchenne muscular dystrophy is a recessive disease due to a mutation in the dystrophin gene. Myoblast transplantation permits to introduce the dystrophin gene in dystrophic muscle fibers. However, the success of this approach is reduced by the short duration of the regeneration following the transplantation, which reduces the number of hybrid fibers. Our aim was to verify whether the success of the myoblast transplantation is enhanced by blocking the myostatin signal with an antagonist, follistatin. Three different approaches were studied to overexpress follistatin in the muscles of mdx mice transplanted with myoblasts. First, transgenic follistatin/mdx mice were generated; second, a follistatin plasmid was electroporated in mdx muscles, and finally, follistatin was induced in mdx mice muscles by a treatment with a histone deacetylase inhibitor. The three approaches improved the success of the myoblast transplantation. Moreover, fiber hypertrophy was also observed in all muscles, demonstrating that myostatin inhibition by follistatin is a good method to improve myoblast transplantation and muscle function. Myostatin inhibition by follistatin in combination with myoblast transplantation is thus a promising novel therapeutic approach for the treatment of muscle wasting in diseases such as Duchenne muscular dystrophy.

【 授权许可】

Unknown   
© 2008 Cognizant Comm. Corp.