Innervation of dystrophic muscle after muscle stem cell therapy |
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Authors: | Matthew Bancone BS Alessandra Sacco PhD Kirkwood E. Personius PT PhD |
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Affiliation: | 1. Department of Rehabilitation Science, School of Public Health and Health Professions, Buffalo, New York, USA;2. Development, Aging and Regeneration Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA;3. Program in Neuroscience, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA |
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Abstract: | 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 |
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Keywords: | denervation Duchenne muscular dystrophy muscle stem cell neuromuscular junction skeletal muscle |
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