Overexpression of Follistatin in Human Myoblasts Increases Their Proliferation and Differentiation, and Improves the Graft Success in SCID Mice

Cell Transplantation

Article

M. Bouchentouf¹  J. P. Tremblay¹  B. F. Benabdallah¹  J. Rousseau¹ 

[1] Génétique humaine, Centre de Recherche du CHUL, Québec, Canada;

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

DOI  :  10.3727/096368909X470865

 received in 2008-07-08, accepted in 2009-01-27,  发布年份 2009

来源: Sage Journals

【 摘 要 】

Duchenne muscular dystrophy is caused by the absence of functional dystrophin, leading to the myofiber membrane instability and progressive muscle atrophy. Myoblast transplantation in dystrophic muscles is a potential therapy, as it permits the long-term restoration of dystrophin expression in transplanted muscles. However, the success of this approach is limited by the short period of muscle repair following myoblast transplantation. Myostatin, a powerful inhibitor of muscle growth, is involved in terminating the period of muscle repair following injury by reducing myoblast proliferation and differentiation. Follistatin forms a complex with myostatin, preventing its interaction with its receptor and thus blocking the myostatin signal. Here, we used a lentivirus to overexpress the follistatin protein in normal myoblasts to block the myostatin signaling. We measured the potential of transduced myoblasts to proliferate and to form multinucleated myotubes in vitro. And finally, we considered the engraftment success of those transduced myoblasts in comparison with control cells in vivo within SCID mice TA muscle. Our results first confirmed the overexpression of follistatin into lentivirus transduced myoblasts, and second showed that the overexpression of the follistatin in normal human myoblasts improved in vitro their proliferation rate by about 1.5-fold after 96 h and also their differentiation rate by about 1.6- and 1.8-fold, respectively, in the absence and in the presence of recombinant myostatin. Finally, our data demonstrated that the engraftment of human normal myoblasts overexpressing the follistatin protein into SCID mouse muscles was enhanced by twofold.

【 授权许可】

Unknown   
© 2009 Cognizant Comm. Corp.

【 图 表 】

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Figure 1b.