Myoexosomes cargo triggers muscle regeneration and provides molecular cues for next-generation therapy in muscular dystrophy

Muscular dystrophies are genetic neuromuscular disorders characterized by skeletal muscle degeneration and consequently enhanced fibrosis. Duchenne muscular dystrophy is the most common form where mutations on the dystrophin gene located on the X chromosome lead to the depletion of the functional protein. Considering the emerging role of extracellular vesiscles in cell-to-cell communication, we hypothesized a beneficial effect on dystrophic muscle of exosomes derived from myogenic cells. This muscle improvement is mainly an enhancement of dystrophic muscle regeneration and it has obtained by the exosomes protein or/and non-coding RNA content. This hypothesis has been validated by the discovery in the muscle-derived exosomes of the full-length and the Dp71 dystrophin isoform and the miRNAs muscle-specific or, at least, involved in regeneration processes. These pro-myogenic effects have been tested in vivo on the dystrophic murine mouse model (mdx) and in vitro on the satellite cells derived from the mdx mouse. These observations highlight the myogenic signature of muscle-derived exosomes and develop new therapeutic strategies for the elucidation of the mechanisms involved in dystrophic muscle progression.