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Open AccessArticle

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

1
Department of Kinesiology and Applied Physiology, University of Delaware, 540 S College Ave, Newark, DE 19713, USA
2
Department of Animal Science, Iowa State University, 2356G Kildee Hall, Ames, IA 50011, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(12), 2544; https://doi.org/10.3390/cells9122544
Received: 21 October 2020 / Revised: 21 November 2020 / Accepted: 23 November 2020 / Published: 26 November 2020
(This article belongs to the Special Issue Stem Cells and Extracellular Vesicles)
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.
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Keywords: muscle stem cells; extracellular vesicles; muscular dystrophy; cachexia; oxidative stress; skeletal muscle; mitochondria muscle stem cells; extracellular vesicles; muscular dystrophy; cachexia; oxidative stress; skeletal muscle; mitochondria
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MDPI and ACS Style

Shuler, K.T.; Wilson, B.E.; Muñoz, E.R.; Mitchell, A.D.; Selsby, J.T.; Hudson, M.B. Muscle Stem Cell-Derived Extracellular Vesicles Reverse Hydrogen Peroxide-Induced Mitochondrial Dysfunction in Mouse Myotubes. Cells 2020, 9, 2544. https://doi.org/10.3390/cells9122544

AMA Style

Shuler KT, Wilson BE, Muñoz ER, Mitchell AD, Selsby JT, Hudson MB. Muscle Stem Cell-Derived Extracellular Vesicles Reverse Hydrogen Peroxide-Induced Mitochondrial Dysfunction in Mouse Myotubes. Cells. 2020; 9(12):2544. https://doi.org/10.3390/cells9122544

Chicago/Turabian Style

Shuler, Kyle T.; Wilson, Brittany E.; Muñoz, Eric R.; Mitchell, Andrew D.; Selsby, Joshua T.; Hudson, Matthew B. 2020. "Muscle Stem Cell-Derived Extracellular Vesicles Reverse Hydrogen Peroxide-Induced Mitochondrial Dysfunction in Mouse Myotubes" Cells 9, no. 12: 2544. https://doi.org/10.3390/cells9122544

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