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These nanosized vesicles possess unique properties such as low immunogenicity and the ability to cross biological barriers, making them ideal carriers for delivering bioactive molecules to injured tissues. MSC-EVs have been demonstrated to exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, and enhancing axonal regeneration. Recent studies have delved into the molecular mechanisms underlying MSC-EV-mediated therapeutic effects. Exosomal microRNAs (miRNAs) have been identified as key regulators of various cellular processes involved in SCI pathogenesis and repair. These miRNAs can influence inflammation, oxidative stress, and apoptosis by modulating gene expression. This review summarized the current state of MSC-EV-based therapies for SCI, highlighting the underlying mechanisms and potential clinical applications. We discussed the challenges and limitations of translating these therapies into clinical practice, such as inconsistent EV production, complex cargo composition, and the need for targeted delivery strategies. Future research should focus on optimizing EV production and characterization, identifying key therapeutic miRNAs, and developing innovative delivery systems to maximize the therapeutic potential of MSC-EVs in SCI.<\/jats:p>","DOI":"10.3390\/ijms26020723","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T09:58:36Z","timestamp":1737021516000},"page":"723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Stem Cell-Derived Extracellular Vesicle-Mediated Therapeutic Signaling in Spinal Cord Injury"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6050-2091","authenticated-orcid":false,"given":"Raju","family":"Poongodi","sequence":"first","affiliation":[{"name":"Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao-Hsiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hsien","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuender D.","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Long-Term Care, MacKay Medical College, New Taipei City 25245, Taiwan"},{"name":"MacKay Children\u2019s Hospital, Taipei 10449, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan"},{"name":"Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2384-7856","authenticated-orcid":false,"given":"Jen-Kun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Anesthesiology, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s13287-024-03758-5","article-title":"Stem cell exosome-loaded Gelfoam improves locomotor dysfunction and neuropathic pain in a rat model of spinal cord injury","volume":"15","author":"Poongodi","year":"2024","journal-title":"Stem Cell Res. 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