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By shuttling bioactive cargoes between cells, they modulate recipient cell behavior, influencing proliferation, differentiation, and tissue remodeling. Previous studies demonstrated that different tensile load regimes can modulate both the production and regenerative capacity of myoblast\u2010derived exosomes, positioning mechanically induced vesicle release as a potential driver of morpho\u2010functional adaptations required for myoblast differentiation and myotube formation. Within this framework, shockwave (SW) therapy is gaining increasing attention as a non\u2010invasive mechanical stimulus in regenerative medicine; however, the precise cellular mechanisms linking SW stimulation and tissue repair remain poorly understood. Preclinical evidence shows that extracellular vesicles (EVs) derived from SW\u2010treated cardiomyocytes possess pro\u2010angiogenic and regenerative properties, suggesting that SW\u2010induced paracrine signaling may be conserved across tissues. In this study, we investigated whether in\u00a0vitro SW treatment affects myogenic exosome release, contributing to SW\u2010mediated muscle regeneration. Tunable Resistive Pore Sensing analysis revealed a significant increase in EV concentration at 6\u2009h post\u2010treatment, with no detectable differences between treated cells and controls at 12\u2009h, indicating a rapid and transient secretory response. Importantly, vesicle size distribution remained unchanged across conditions, suggesting that SW primarily modulates EV production dynamics rather than vesicle morphology. Ultrastructural analyses further confirmed this transient activation, showing vesicular trafficking and exosome\u2010like EV secretion in treated myoblasts. Further mechanistic insights into SW\u2010induced exosome release may uncover novel pathways, contributing to SW regenerative effects supporting its translational application to muscle injuries and disorders.<\/jats:p>","DOI":"10.1096\/fj.202603103r","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:03:23Z","timestamp":1786979003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Shockwave\u2010Induced Myoblast Exosome\u2010Like Vesicles: Emerging Drivers of Muscle Regeneration"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3150-1863","authenticated-orcid":false,"given":"Larisa","family":"Ryskalin","sequence":"first","affiliation":[{"name":"Department of Translational Research and New Technologies Medicine and Surgery University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-1218","authenticated-orcid":false,"given":"Federica","family":"Fulceri","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies Medicine and Surgery University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Germelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"D'Agostino","sequence":"additional","affiliation":[{"name":"Ortho\u2010Rehabilitation Department Shock Waves Center, IRCCS Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Soldani","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies Medicine and Surgery University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Da Pozzo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Gesi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies Medicine and Surgery University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40634\u2010016\u20100051\u20107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051297"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbaf050"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40373"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1984879"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203654200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00595.2001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1191035"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1517517113"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcot.2020.02.004"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/life15121912"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz209"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.779936"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201000104\u20104"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010019\u20100282\u20102"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2020.34.s1.02173"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073869"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25115811"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084153"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211\u20105463.13504"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.12.018"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3791\/51076"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2025.1636931"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.03.007"},{"key":"e_1_2_7_26_1","volume-title":"Ultrastructural Pathology of the Cell and Matrix","author":"Ghadially F. 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