{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:45:36Z","timestamp":1788385536287,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Stroke is a leading cause of death and disability. The therapeutic potential of mesenchymal stem cell\u2010derived extracellular vesicles (MSC\u2010EVs) has shown considerable promise in rodent models of stroke. However, the therapeutic efficacy and safety of clinical\u2010scale MSC\u2010EVs for ischemic stroke are not well elucidated, especially in non\u2010human primates. We developed a scalable production method for MSC\u2010EVs using a 3D bioprocessing platform. EVs were isolated with a filter and tangential flow filtration and characterized using electron microscopy, nanoparticle tracking analysis, nanoflow cytometry analysis, proteomic and lipidomic analysis using mass spectrometry, and RNA sequencing. We determined the appropriate dosage and frequency of intravenous administration of EVs in a mouse stroke model. A biodistribution study of the selected dose regimen was performed using the internal cargo of EVs, human mitochondrial DNA. We then confirmed the efficacy of EVs in a marmoset stroke model. Improvement in behavioural tests and MRI\u2010based neuroplasticity were compared between the control and EV groups through blinded evaluation. The proteome profiles of the infarcted hemisphere were also evaluated. EV products showed suitable lot\u2010to\u2010lot consistency. In a mouse stroke model, intravenous administration of a dose of 6 \u00d7 10\n                    <jats:sup>8<\/jats:sup>\n                    EVs for 5 days resulted in the smallest infarct volume and improvement in motor function. A biodistribution study showed that EVs were rapidly distributed into systemic organs and were relatively specifically distributed to the infarcted brain areas. Intravenous administration of an equivalent dose (3.5 \u00d7 10\n                    <jats:sup>9<\/jats:sup>\n                    EVs for 5 days) in a marmoset stroke model significantly improved motor functions and anatomical connectivity on diffusion MRI, and significantly reduced infarct volume. Proteomics analyses indicated that EV treatment promoted neurogenesis, synapse organization, and vascular development. In conclusion, this study is the first to demonstrate that a clinical\u2010scale EV product is safe and significantly enhances function recovery and neuroplasticity in a non\u2010human primate stroke model, offering a promising treatment for human stroke.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70110","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T03:50:03Z","timestamp":1750650603000},"source":"Crossref","is-referenced-by-count":20,"title":["Clinical Scale MSC\u2010Derived Extracellular Vesicles Enhance Poststroke Neuroplasticity in Rodents and Non\u2010Human Primates"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1580-3204","authenticated-orcid":false,"given":"Eun Hee","family":"Kim","sequence":"first","affiliation":[{"name":"S&amp;E bio Co., Ltd. Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8655-3495","authenticated-orcid":false,"given":"Jeong Pyo","family":"Son","sequence":"additional","affiliation":[{"name":"Accelerator Radioisotope Research Section Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI) Jeongeup South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyun Sik","family":"Oh","sequence":"additional","affiliation":[{"name":"S&amp;E bio Co., Ltd. Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suji","family":"Park","sequence":"additional","affiliation":[{"name":"S&amp;E bio Co., Ltd. Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunchong","family":"Hong","sequence":"additional","affiliation":[{"name":"Non\u2010Clinical Evaluation Center (NCC) Osong Medical Innovation Foundation Cheongju South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung\u2010Sun","family":"Lee","sequence":"additional","affiliation":[{"name":"Non\u2010Clinical Evaluation Center (NCC) Osong Medical Innovation Foundation Cheongju South\u00a0Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chopp","sequence":"additional","affiliation":[{"name":"Department of Neurology Henry Ford Health Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7962-8751","authenticated-orcid":false,"given":"Oh Young","family":"Bang","sequence":"additional","affiliation":[{"name":"S&amp;E bio Co., Ltd. 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