Innervation of dystrophic muscle after muscle stem cell therapy

Introduction: Duchenne muscular dystrophy (DMD) is caused by loss of the structural protein, dystrophin, resulting in muscle fragility. Muscle stem cell (MuSC) transplantation is a potential therapy for DMD. It is unknown whether donor-derived muscle fibers are structurally innervated. Methods: Green fluorescent protein (GFP)–expressing MuSCs were transplanted into the tibials anterior of adult dystrophic mdx/mTR mice. Three weeks later the neuromuscular junction was labeled by immunohistochemistry. Results: The percent overlap between pre- and postsynaptic immunolabeling was greater in donor-derived GFP⁺ myofibers, and fewer GFP⁺ myofibers were identified as denervated compared with control GFP^– fibers (P = 0.001 and 0.03). GFP⁺ fibers also demonstrated acetylcholine receptor fragmentation and expanded endplate area, indicators of muscle reinnervation (P = 0.008 and 0.033). Conclusion: It is unclear whether GFP⁺ fibers are a result of de novo synthesis or fusion with damaged endogenous fibers. Either way, donor-derived fibers demonstrate clear histological innervation. Muscle Nerve 54: 763–768, 2016.