{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:28:57Z","timestamp":1790512137583,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01 NS102157"],"award-info":[{"award-number":["NIH R01 NS102157"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH P20 GM113125"],"award-info":[{"award-number":["NIH P20 GM113125"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH P20 GM103446"],"award-info":[{"award-number":["NIH P20 GM103446"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R03 HD094594"],"award-info":[{"award-number":["NIH R03 HD094594"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells9122544","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T22:00:33Z","timestamp":1606428033000},"page":"2544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Muscle Stem Cell-Derived Extracellular Vesicles Reverse Hydrogen Peroxide-Induced Mitochondrial Dysfunction in Mouse Myotubes"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-4714","authenticated-orcid":false,"given":"Kyle T.","family":"Shuler","sequence":"first","affiliation":[{"name":"Department of Kinesiology and Applied Physiology, University of Delaware, 540 S College Ave, Newark, DE 19713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany E.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Applied Physiology, University of Delaware, 540 S College Ave, Newark, DE 19713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-7513","authenticated-orcid":false,"given":"Eric R.","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Applied Physiology, University of Delaware, 540 S College Ave, Newark, DE 19713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Applied Physiology, University of Delaware, 540 S College Ave, Newark, DE 19713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua T.","family":"Selsby","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Iowa State University, 2356G Kildee Hall, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Hudson","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Applied Physiology, University of Delaware, 540 S College Ave, Newark, DE 19713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nrm3265","article-title":"Satellite cells, the engines of muscle repair","volume":"13","author":"Wang","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/2044-5040-3-2","article-title":"Satellite cell therapy\u2013from mice to men","volume":"3","author":"Bareja","year":"2013","journal-title":"Skelet. Muscle"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/ALN.0000000000000245","article-title":"Inhibition of the ubiquitin-proteasome pathway does not protect against ventilator-induced accelerated proteolysis or atrophy in the diaphragm","volume":"121","author":"Smuder","year":"2014","journal-title":"Anesthesiology"},{"key":"ref_4","first-page":"e50846","article-title":"Isolation, Culture, and Transplantation of Muscle Satellite Cells","volume":"86","author":"Motohashi","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.stemcr.2018.01.022","article-title":"High-Yield Purification, Preservation, and Serial Transplantation of Human Satellite Cells","volume":"10","author":"Garcia","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1038\/s41598-017-03703-y","article-title":"Human myogenic reserve cells are quiescent stem cells that contribute to muscle regeneration after intramuscular transplantation in immunodeficient mice","volume":"7","author":"Laumonier","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.semcdb.2015.09.009","article-title":"Impaired regeneration: A role for the muscle microenvironment in cancer cachexia","volume":"54","author":"Talbert","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/MCO.0000000000000409","article-title":"Altered satellite cell dynamics accompany skeletal muscle atrophy during chronic illness, disuse, and aging","volume":"20","author":"McKenna","year":"2017","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1097\/ALN.0b013e31829b3692","article-title":"Negative Pressure Ventilation and Positive Pressure Ventilation Promote Comparable Levels of Ventilator-induced Diaphragmatic Dysfunction in Rats","volume":"119","author":"Bruells","year":"2013","journal-title":"Anesthesiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1097\/CCM.0b013e31823c8cc9","article-title":"Both high level pressure support ventilation and controlled mechanical ventilation induce diaphragm dysfunction and atrophy","volume":"40","author":"Hudson","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1378\/chest.09-2787","article-title":"Mechanical ventilation-induced oxidative stress in the diaphragm: Role of heme oxygenase-1","volume":"139","author":"Falk","year":"2011","journal-title":"Chest"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rahnert, J.A., Zheng, B., Hudson, M.B., Woodworth-Hobbs, M.E., and Price, S.R. (2016). Glucocorticoids Alter CRTC-CREB Signaling in Muscle Cells: Impact on PGC-1alpha Expression and Atrophy Markers. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159181"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.jnutbio.2014.03.017","article-title":"Docosahexaenoic acid prevents palmitate-induced activation of proteolytic systems in C2C12 myotubes","volume":"25","author":"Hudson","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1089\/hum.2015.139","article-title":"Cellular Therapies for Muscular Dystrophies: Frustrations and Clinical Successes","volume":"27","author":"Negroni","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1517\/14712598.2015.1057564","article-title":"Cell therapy in muscular dystrophies: Many promises in mice and dogs, few facts in patients","volume":"15","author":"Skuk","year":"2015","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_16","first-page":"117","article-title":"Isolation and purification of satellite cells for skeletal muscle tissue engineering","volume":"3","author":"Syverud","year":"2014","journal-title":"J. Regen. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz, E.R., Caccese, J.B., Wilson, B.E., Shuler, K.T., Santos, F.V., Cab\u00e1n, C.T., Jeka, J.J., Langford, D., and Hudson, M.B. (2020). Effects of purposeful soccer heading on circulating small extracellular vesicle concentration and cargo. J. Sport Health Sci., in press.","DOI":"10.1016\/j.jshs.2020.11.006"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C551","DOI":"10.1152\/ajpcell.00266.2013","article-title":"miR-23a is decreased during muscle atrophy by a mechanism that includes calcineurin signaling and exosome-mediated export","volume":"306","author":"Hudson","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7309","DOI":"10.4049\/jimmunol.166.12.7309","article-title":"Proteomic analysis of dendritic cell-derived exosomes: A secreted subcellular compartment distinct from apoptotic vesicles","volume":"166","author":"Boussac","year":"2001","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mam.2018.02.002","article-title":"Subpopulations of extracellular vesicles and their therapeutic potential","volume":"60","author":"Lasser","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"C314","DOI":"10.1152\/ajpcell.00395.2013","article-title":"miR-182 attenuates atrophy-related gene expression by targeting FoxO3 in skeletal muscle","volume":"307","author":"Hudson","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.stem.2016.09.010","article-title":"Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy","volume":"20","author":"Fry","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3389\/fphar.2018.00152","article-title":"Extracellular Guanosine 5\u2032-Triphosphate Induces Human Muscle Satellite Cells to Release Exosomes Stuffed With Guanosine","volume":"9","author":"Pietrangelo","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_24","unstructured":"Hettinger, Z.R. (2018). Effects of Oxidative Stress on Exosome Release in Human Skeletal Muscle Satellite Cells, ProQuest Dissertations Publishing."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"zqaa009","DOI":"10.1093\/function\/zqaa009","article-title":"Fusion-Independent Satellite Cell Communication to Muscle Fibers During Load-Induced Hypertrophy","volume":"1","author":"Murach","year":"2020","journal-title":"Function"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1002\/sctm.19-0447","article-title":"Skeletal muscle stem cells confer maturing macrophages anti-inflammatory properties through insulin-like growth factor-2","volume":"9","author":"Fang","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.stemcr.2018.01.023","article-title":"Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy","volume":"10","author":"Aminzadeh","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.1096\/fj.11-203232","article-title":"Induction of muscle regeneration by RNA-mediated mitochondrial restoration","volume":"26","author":"Jash","year":"2012","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E802","DOI":"10.1152\/ajpendo.00343.2001","article-title":"Mitochondrial biogenesis during skeletal muscle regeneration","volume":"282","author":"Duguez","year":"2002","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pant, M., Sopariwala, D.H., Bal, N.C., Lowe, J., Delfin, D.A., Rafael-Fortney, J., and Periasamy, M. (2015). Metabolic dysfunction and altered mitochondrial dynamics in the utrophin-dystrophin deficient mouse model of duchenne muscular dystrophy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123875"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1113\/JP277306","article-title":"Impairments in left ventricular mitochondrial bioenergetics precede overt cardiac dysfunction and remodelling in Duchenne muscular dystrophy","volume":"598","author":"Hughes","year":"2019","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e12944","DOI":"10.1111\/apha.12944","article-title":"Autophagic dysfunction and autophagosome escape in the mdx mus musculus model of Duchenne muscular dystrophy","volume":"222","author":"Spaulding","year":"2018","journal-title":"Acta Physiol."},{"key":"ref_33","first-page":"160","article-title":"Prolonged environment-induced hyperthermia alters autophagy in oxidative skeletal muscle in Sus scrofa","volume":"74","author":"Ganesan","year":"2018","journal-title":"J. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1002\/jcsm.12232","article-title":"Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice","volume":"8","author":"Brown","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.abb.2018.11.005","article-title":"Mitochondrial dysfunction induces muscle atrophy during prolonged inactivity: A review of the causes and effects","volume":"662","author":"Hyatt","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E31","DOI":"10.1152\/ajpendo.00609.2011","article-title":"Mitochondrial signaling contributes to disuse muscle atrophy","volume":"303","author":"Powers","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1097\/CCM.0b013e3182190b62","article-title":"Mitochondria-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness","volume":"39","author":"Powers","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hudson, M.B., Smuder, A.J., Nelson, W.B., Wiggs, M.P., Shimkus, K.L., Fluckey, J.D., Szeto, H.H., and Powers, S.K. (2015). Partial Support Ventilation and Mitochondrial-Targeted Antioxidants Protect against Ventilator-Induced Decreases in Diaphragm Muscle Protein Synthesis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137693"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.freeradbiomed.2017.11.025","article-title":"Crosstalk between autophagy and oxidative stress regulates proteolysis in the diaphragm during mechanical ventilation","volume":"115","author":"Smuder","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1152\/japplphysiol.01086.2011","article-title":"Endurance exercise attenuates ventilator-induced diaphragm dysfunction","volume":"112","author":"Smuder","year":"2012","journal-title":"J. Appl. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.freeradbiomed.2009.01.002","article-title":"Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production","volume":"46","author":"Kavazis","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.freeradbiomed.2010.12.009","article-title":"Exercise-induced oxidative stress in humans: Cause and consequences","volume":"51","author":"Powers","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1515\/hsz-2012-0247","article-title":"Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy","volume":"394","author":"Calvani","year":"2013","journal-title":"Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bone.2019.05.021","article-title":"The clinical impact and biological mechanisms of skeletal muscle aging","volume":"127","author":"Aversa","year":"2019","journal-title":"Bone"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1113\/EP088096","article-title":"Alterations in mitochondrial functions and morphology in muscle and non-muscle tissues in type 1 diabetes: Implications for metabolic health","volume":"105","author":"Monaco","year":"2020","journal-title":"Exp. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Carre, J.E., and Affourtit, C. (2019). Mitochondrial Activity and Skeletal Muscle Insulin Resistance in Kidney Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112751"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"F1128","DOI":"10.1152\/ajprenal.00600.2016","article-title":"Chronic kidney disease induces autophagy leading to dysfunction of mitochondria in skeletal muscle","volume":"312","author":"Su","year":"2017","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3389\/fphys.2016.00403","article-title":"Skeletal Muscle Satellite Cells, Mitochondria, and MicroRNAs: Their Involvement in the Pathogenesis of ALS","volume":"7","author":"Tsitkanou","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1093\/gerona\/63.6.566","article-title":"Sca-1-expressing nonmyogenic cells contribute to fibrosis in aged skeletal muscle","volume":"63","author":"Hidestrand","year":"2008","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.celrep.2019.12.100","article-title":"Heterogeneity of Satellite Cells Implicates DELTA1\/NOTCH2 Signaling in Self-Renewal","volume":"30","author":"Yartseva","year":"2020","journal-title":"Cell Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1242\/dev.144089","article-title":"BMP signaling regulates satellite cell-dependent postnatal muscle growth","volume":"144","author":"Stantzou","year":"2017","journal-title":"Development"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5980465","DOI":"10.1155\/2019\/5980465","article-title":"Metformin delays satellite cell activation and maintains quiescence","volume":"2019","author":"Pavlidou","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1097\/CCM.0b013e31819cef63","article-title":"Apocynin attenuates diaphragm oxidative stress and protease activation during prolonged mechanical ventilation","volume":"37","author":"McClung","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1596016","DOI":"10.1080\/20013078.2019.1596016","article-title":"Extracellular vesicle measurements with nanoparticle tracking analysis-An accuracy and repeatability comparison between NanoSight NS300 and ZetaView","volume":"8","author":"Bachurski","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1089\/hum.2018.151","article-title":"Gene and Cell Therapy for Muscular Dystrophies: Are We Getting There?","volume":"29","author":"Galli","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev-pharmtox-061616-030146","article-title":"Stem Cell Extracellular Vesicles: Extended Messages of Regeneration","volume":"57","author":"Riazifar","year":"2017","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3389\/fimmu.2018.01011","article-title":"Monitoring extracellular Vesicle Cargo Active Uptake by Imaging Flow Cytometry","volume":"9","author":"Rudik","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8856","DOI":"10.1038\/s41598-020-65517-9","article-title":"In vitro cultured human endometrial cells release extracellular vesicles that can be uptaken by spermatozoa","volume":"10","author":"Murdica","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"24641","DOI":"10.3402\/jev.v3.24641","article-title":"Routes and mechanisms of extracellular vesicle uptake","volume":"3","author":"Mulcahy","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"30087","DOI":"10.3402\/jev.v4.30087","article-title":"Applying extracellular vesicles based therapeutics in clinical trials-an ISEV position paper","volume":"4","author":"Lener","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13287-019-1534-0","article-title":"Influence of mesenchymal stem cell-derived extracellular vesicles in vitro and their role in ageing","volume":"11","author":"Arntz","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3389\/fbioe.2019.00292","article-title":"Hypoxia Conditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Induce Increased Vascular Tube Formation in vitro","volume":"7","author":"Almeria","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15885","DOI":"10.1038\/s41598-018-34357-z","article-title":"Endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning","volume":"8","author":"Davidson","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"11942","DOI":"10.1039\/c2cc36111f","article-title":"A label-free electrical detection of exosomal microRNAs using microelectrode array","volume":"48","author":"Goda","year":"2012","journal-title":"Chem. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"834","DOI":"10.3892\/ijmm.2017.3080","article-title":"Comparison of isolation methods of exosomes and exosomal RNA from cell culture medium and serum","volume":"40","author":"Tang","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/s41598-020-57497-7","article-title":"A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum","volume":"10","author":"Brennan","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"a008706","DOI":"10.1101\/cshperspect.a008706","article-title":"Mitochondrial Regulation of Cell Death","volume":"5","author":"Tait","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/cdd.2016.127","article-title":"Mitochondria mediate cell membrane repair and contribute to Duchenne muscular dystrophy","volume":"24","author":"Maria","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"886","DOI":"10.3892\/ijo.2013.1998","article-title":"Skeletal muscle mitochondrial uncoupling in a murine cancer cachexia model","volume":"43","author":"Tzika","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2044-5040-1-4","article-title":"Regulation of skeletal muscle growth by the IGF1-Akt\/PKB pathway: Insights from genetic models","volume":"1","author":"Schiaffino","year":"2011","journal-title":"Skelet. Muscle"},{"key":"ref_73","first-page":"34","article-title":"Protein breakdown in muscle wasting: Role of the autophagy-lysosome and ubiquitin-proteasome pathways","volume":"210","author":"Sandri","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1042\/bj20030200","article-title":"Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo","volume":"373","author":"Meirhaeghe","year":"2003","journal-title":"Biochem. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.cmet.2006.06.005","article-title":"Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation (vol 3, pg 333, 2006)","volume":"4","author":"Uldry","year":"2006","journal-title":"Cell Metab."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Selsby, J.T., Morine, K.J., Pendrak, K., Barton, E.R., and Sweeney, H.L. (2012). Rescue of Dystrophic Skeletal Muscle by PGC-1 alpha Involves a Fast to Slow Fiber Type Shift in the mdx Mouse. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030063"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"16519","DOI":"10.1038\/s41598-018-34879-6","article-title":"Exosomes exert cardioprotection in dystrophin-deficient cardiomyocytes via ERK1\/2-p38\/MAPK signaling","volume":"8","author":"Gartz","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nature18928","article-title":"Transfer of mitochondria from astrocytes to neurons after stroke","volume":"535","author":"Hayakawa","year":"2016","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3389\/fgene.2017.00177","article-title":"Mitochondria: A Common Target for Genetic Mutations and Environmental Toxicants in Parkinson\u2019s Disease","volume":"8","author":"Helley","year":"2017","journal-title":"Front. Genet."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/12\/2544\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:37:40Z","timestamp":1760179060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/12\/2544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,26]]},"references-count":79,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["cells9122544"],"URL":"https:\/\/doi.org\/10.3390\/cells9122544","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.03.04.977280","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,26]]}}}