Long-term engraftment of myogenic progenitors from adipose-derived stem cells and muscle regeneration in dystrophic mice

Abstract

Stem cell therapy is a promising approach for treating Duchenne muscular dystrophy (DMD); however, its application is hindered by poor cell engraftment. There have been no reports to date describing the efficient generation of myogenic progenitors fromadipose-derived stem cells (ADSCs) that can contribute to muscle regeneration. In this study, we examined the in vivo myogenic potential of progenitors differentiated from ADSCs using forskolin, basic fibroblast growth factor, the glycogen synthase kinase 3ß inhibitor 6-bromoindirubin-3'-oxime aswell as the supernatant of ADSC cultures. The results indicate that a proliferative population of myogenic progenitors can be derived fromADSCs that have characteristics similar to muscle satellite cells and are capable of terminal differentiation into multinucleated myotubes. When transplanted into DMD model mdx mice either by intramuscular injection or systemic delivery, progenitors were successfully engrafted in skeletal muscle for up to 12 weeks, and generated new muscle fibers, restored dystrophin expression and contributed to the satellite cell compartment. These findings highlight the potential application of myogenic progenitors derived from ADSCs to the treatment of muscular dystrophy.