{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:49:21Z","timestamp":1790833761357,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2019-07196"],"award-info":[{"award-number":["RGPIN-2019-07196"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interrupted blood flow in the brain due to ischemic injuries such as ischemic stroke or traumatic brain injury results in irreversible brain damage, leading to cognitive impairment associated with inflammation, disruption of the blood\u2013brain barrier (BBB), and cell death. Since the BBB only allows entry to a small class of drugs, many drugs used to treat ischemia in other tissues have failed in brain-related disorders. The administration of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) has shown promise in improving the functional recovery of the brain following cerebral ischemia by inducing blood vessel formation. To facilitate such a treatment approach, it is necessary to develop bioprocesses that can produce therapeutically relevant MSC-EVs in a reproducible and scalable manner. This study evaluated the feasibility of using stirred suspension bioreactors (SSBs) to scale-up the serum-free production of pro-angiogenic MSC-EVs under clinically relevant physioxic conditions. It was found that MSCs grown in SSBs generated EVs that stimulated angiogenesis in cerebral microvascular endothelial cells, supporting the use of SSBs to produce MSC-EVs for application in cerebral ischemia. These properties were impaired at higher cell confluency, outlining the importance of considering the time of harvest when developing bioprocesses to manufacture EV populations.<\/jats:p>","DOI":"10.3390\/ijms25105219","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:03:08Z","timestamp":1715673788000},"page":"5219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Extracellular Vesicles Generated by Mesenchymal Stem Cells in Stirred Suspension Bioreactors Promote Angiogenesis in Human-Brain-Derived Endothelial Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4834-1547","authenticated-orcid":false,"given":"Jolene","family":"Phelps","sequence":"first","affiliation":[{"name":"Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, AB T2N 1N4, Canada"},{"name":"Department of Biomedical Engineering, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, AB T2N 1N4, Canada"},{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive N.W., Calgary, AB T2N 4Z6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-294X","authenticated-orcid":false,"given":"David A.","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, AB T2N 1N4, Canada"},{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive N.W., Calgary, AB T2N 4Z6, Canada"},{"name":"Department of Surgery, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, Canada"},{"name":"Faculty of Kinesiology, University of Calgary, 2500 University Drive N.W., Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alim P.","family":"Mitha","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, AB T2N 1N4, Canada"},{"name":"Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, 1403 29 Street N.W., Calgary, AB T2N 2T9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Duncan","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive N.W., Calgary, AB T2N 4Z6, Canada"},{"name":"Department of Surgery, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, Canada"},{"name":"Department of Civil Engineering, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8994-8601","authenticated-orcid":false,"given":"Arindom","family":"Sen","sequence":"additional","affiliation":[{"name":"Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, AB T2N 1N4, Canada"},{"name":"Department of Biomedical Engineering, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, AB T2N 1N4, Canada"},{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive N.W., Calgary, AB T2N 4Z6, Canada"},{"name":"Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"ref_1","unstructured":"Clarke, D.D., and Sokoloff, L. 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