Muscle Stem Cell-Derived Extracellular Vesicles Reverse Hydrogen Peroxide-Induced Mitochondrial Dysfunction in Mouse Myotubes

Cells

卷:9

JoshuaT. Selsby¹  KyleT. Shuler²  EricR. Muñoz²  MatthewB. Hudson²  BrittanyE. Wilson²  AndrewD. Mitchell² 

[1] Department of Animal Science, Iowa State University, 2356G Kildee Hall, Ames, IA 50011, USA;

[2] Department of Kinesiology and Applied Physiology, University of Delaware, 540 S College Ave, Newark, DE 19713, USA;

关键词: muscle stem cells;    extracellular vesicles;    muscular dystrophy;    cachexia;    oxidative stress;    skeletal muscle;   

DOI  :  10.3390/cells9122544

来源: DOAJ

【 摘 要 】

Muscle stem cells (MuSCs) hold great potential as a regenerative therapeutic but have met numerous challenges in treating systemic muscle diseases. Muscle stem cell-derived extracellular vesicles (MuSC-EVs) may overcome these limitations. We assessed the number and size distribution of extracellular vesicles (EVs) released by MuSCs ex vivo, determined the extent to which MuSC-EVs deliver molecular cargo to myotubes in vitro, and quantified MuSC-EV-mediated restoration of mitochondrial function following oxidative injury. MuSCs released an abundance of EVs in culture. MuSC-EVs delivered protein cargo into myotubes within 2 h of incubation. Fluorescent labeling of intracellular mitochondria showed co-localization of delivered protein and mitochondria. Oxidatively injured myotubes demonstrated a significant decline in maximal oxygen consumption rate and spare respiratory capacity relative to untreated myotubes. Remarkably, subsequent treatment with MuSC-EVs significantly improved maximal oxygen consumption rate and spare respiratory capacity relative to the myotubes that were damaged but received no subsequent treatment. Surprisingly, MuSC-EVs did not affect mitochondrial function in undamaged myotubes, suggesting the cargo delivered is able to repair but does not expand the existing mitochondrial network. These data demonstrate that MuSC-EVs rapidly deliver proteins into myotubes, a portion of which co-localizes with mitochondria, and reverses mitochondria dysfunction in oxidatively-damaged myotubes.

【 授权许可】

Unknown