Several obstacles remain in the translation of muscle stem cell therapies to the clinic. First, our understanding of the precise molecular basis that differentiates self-renewing multipotent stem cells from progenitors that cannot engraft muscle fibers remains insufficient. We anticipate further work in this area to yield important breakthroughs on the mechanisms controlling the regenerative potential of MuSCs.

Second, culture systems have primarily been optimized using mouse MuSCs, and whether these same approaches can be applied to human MuSCs remains to be confirmed—especially since human and mouse MuSCs have distinct functional properties. Third, the transition to the clinic

will ultimately require more regulatory-compliant reagents, such as serum-free media and chemically defined culture systems. Substituting components such as animal serum is not straightforward and represents a major biological hurdle to generating clinical-grade cells under current good manufacturing practices (cGMP).

Finally, the recently approved CAR-T therapies clearly demonstrate that personalized medicine approaches can be incredibly expensive due to the inherent fixed costs of generating patient-specific cells. Issues related to the affordability and anticipated efficacy of cell therapy strategies should be considered against the backdrop of recent, competing developments in, for example, AAV-mediated gene therapies and CRSPR-based gene correction approaches for muscular dystrophy, which have also shown tremendous promise in correcting genetic defects in preclinical myopathy models and are entering the clinic.