{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T23:18:18Z","timestamp":1784243898508,"version":"3.55.0"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker.<\/jats:p>","DOI":"10.1093\/stcltm\/szae072","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T18:33:12Z","timestamp":1728930792000},"page":"1043-1052","source":"Crossref","is-referenced-by-count":17,"title":["Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2966-9782","authenticated-orcid":false,"given":"Cesar V","family":"Borlongan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine , Tampa, FL 33612 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jea-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine , Tampa, FL 33612 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"D\u2019Egidio","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine , Tampa, FL 33612 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"de Kalbermatten","sequence":"additional","affiliation":[{"name":"CellProthera , 12 Rue du Parc, 68100 Mulhouse ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibon","family":"Garitaonandia","sequence":"additional","affiliation":[{"name":"CellProthera , 12 Rue du Parc, 68100 Mulhouse 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