{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:00:03Z","timestamp":1784890803502,"version":"3.55.0"},"reference-count":199,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T00:00:00Z","timestamp":1631836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["110-2314-B-038-099"],"award-info":[{"award-number":["110-2314-B-038-099"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["109-2314-B-038-050"],"award-info":[{"award-number":["109-2314-B-038-050"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic stroke is the leading cause of mortality and long-term disability worldwide. Disruption of the blood\u2013brain barrier (BBB) is a prominent pathophysiological mechanism, responsible for a series of subsequent inflammatory cascades that exacerbate the damage to brain tissue. However, the benefit of recanalization is limited in most patients because of the narrow therapeutic time window. Recently, mesenchymal stem cells (MSCs) have been assessed as excellent candidates for cell-based therapy in cerebral ischemia, including neuroinflammatory alleviation, angiogenesis and neurogenesis promotion through their paracrine actions. In addition, accumulating evidence on how MSC therapy preserves BBB integrity after stroke may open up novel therapeutic targets for treating cerebrovascular diseases. In this review, we focus on the molecular mechanisms of MSC-based therapy in the ischemia-induced prevention of BBB compromise. Currently, therapeutic effects of MSCs for stroke are primarily based on the fundamental pathogenesis of BBB breakdown, such as attenuating leukocyte infiltration, matrix metalloproteinase (MMP) regulation, antioxidant, anti-inflammation, stabilizing morphology and crosstalk between cellular components of the BBB. We also discuss prospective studies to improve the effectiveness of MSC therapy through enhanced migration into defined brain regions of stem cells. Targeted therapy is a promising new direction and is being prioritized for extensive research.<\/jats:p>","DOI":"10.3390\/ijms221810045","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T21:23:29Z","timestamp":1631913809000},"page":"10045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Mesenchymal Stem\/Stromal Cell Therapy in Blood\u2013Brain Barrier Preservation Following Ischemia: Molecular Mechanisms and Prospects"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4882-8339","authenticated-orcid":false,"given":"Phuong Thao","family":"Do","sequence":"first","affiliation":[{"name":"International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Pediatrics, Hanoi Medical University, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Che","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"TMU Neuroscience Research Center, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Neuroscience Institute, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Hsiao","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"TMU Neuroscience Research Center, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Neuroscience Institute, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4900-5967","authenticated-orcid":false,"given":"Chaur-Jong","family":"Hu","sequence":"additional","affiliation":[{"name":"TMU Neuroscience Research Center, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Neuroscience Institute, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Neurology and Stroke Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"TMU Neuroscience Research Center, Taipei Medical University, Taipei 110, Taiwan"},{"name":"The PhD Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics\u20142020 Update: A Report from the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1474-4422(19)30034-1","article-title":"Global, regional, and national burden of stroke, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Johnson","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_3","first-page":"644","article-title":"Injury and repair mechanisms in ischemic stroke: Considerations for the development of novel neurotherapeutics","volume":"10","year":"2009","journal-title":"Curr. 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