{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:01:23Z","timestamp":1789041683475,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The University of Georgia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor neuron degeneration and muscle atrophy, with no effective treatments available. Chronic inflammation, which impairs muscle regeneration and promotes proteolysis, is a key contributor to ALS-related muscle atrophy and a promising therapeutic target. Here, we applied extracellular vesicles (EVs) derived from regenerating skeletal muscles 14 days post-acute injury (CTXD14SkM-EVs), which possess a unique anti-inflammatory profile, to target muscle defects in ALS. We found that CTXD14SkM-EVs enhanced myoblast differentiation and fusion in a cellular muscle-wasting model induced by pro-inflammatory cytokine tumor necrosis factor alpha. Intramuscular administration of these EVs into an ALS mouse model mitigated muscle atrophy by promoting muscle regeneration, shifting macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 state, and suppressing the aberrant Nuclear Factor Kappa B (NF-\u03baB) signaling, a key driver of muscle protein degradation. These results underscore the therapeutic potential of regenerating muscle-derived EVs for combating muscle atrophy in ALS.<\/jats:p>","DOI":"10.3390\/cells14060464","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T09:17:39Z","timestamp":1742462259000},"page":"464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Jinghui","family":"Gao","sequence":"first","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1176-3005","authenticated-orcid":false,"given":"Aria","family":"Sikal","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Hankin","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1646-5964","authenticated-orcid":false,"given":"Yaochao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elijah","family":"Sterling","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8851-7885","authenticated-orcid":false,"given":"Yao","family":"Yao","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: A clinical review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur. 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