Journal
MOLECULAR THERAPY
Volume 29, Issue 4, Pages 1459-1470Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2020.12.018
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Funding
- National Key R&D Program of China [2017YFC1001902]
- National Natural Science Foundation of China [81672124, 81900882, 81802124, 81671528]
- Tianjin Municipal 13th 5-year plan (Tianjin Medical University Talent Project)
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Duchenne muscular dystrophy (DMD) is a genetic disorder that compromises cellular membranes, but the use of exosomes can improve muscle membrane integrity, leading to functional improvements in DMD patients.
Duchenne muscular dystrophy (DMD) is a devastating genetic disorder that leads to compromised cellular membranes, caused by the absence of membrane-bound dystrophin protein. Muscle membrane leakage results in disrupted intracellular homeostasis, protein degradation, and muscle wasting. Improving muscle membrane integrity may delay disease progression and extend the lifespan of DMD patients. Here, we demonstrate that exosomes, membranous extracellular vesicles, can elicit functional improvements in dystrophic mice by improving muscle membrane integrity. Systemic administration of exosomes from different sources induced phenotypic rescue and mitigated pathological progression in dystrophic mice without detectable toxicity. Improved membrane integrity conferred by exosomes inhibited intracellular calcium influx and calcium-dependent activation of calpain proteases, preventing the degradation of the destabilized dystrophin-associated protein complex. We show that exosomes, particularly myotube-derived exosomes, induced functional improvements and alleviated muscle deterioration by stabilizing damaged muscle membrane in dystrophic mice. Our findings suggest that exosomes may have therapeutic implications for DMD and other diseases with compromised membranes.
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