{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:33:21Z","timestamp":1790858001686,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare","award":["HI16C1559"],"award-info":[{"award-number":["HI16C1559"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although intravenous administration of mesenchymal stem cells (MSCs) is effective for experimental stroke, low engraftment and the limited functional capacity of transplanted cells are critical hurdles for clinical applications. C\u2013C motif chemokine ligand 2 (CCL2) is associated with neurological repair after stroke and delivery of various cells into the brain via CCL2\/CCR2 (CCL2 receptor) interaction. In this study, after CCL2-overexpressing human umbilical cord-derived MSCs (hUC-MSCs) were intravenously transplanted with mannitol in rats with middle cerebral arterial occlusion, we compared the differences between four different treatment groups: mannitol + CCL2-overexpressing hUC-MSCs (CCL2-MSC), mannitol + na\u00efve hUC-MSCs (M-MSC), mannitol only, and control. At four-weeks post-transplantation, the CCL2-MSC group showed significantly better functional recovery and smaller stroke volume relative to the other groups. Additionally, we observed upregulated levels of CCR2 in acute ischemic brain and the increase of migrated stem cells into these areas in the CCL2-MSC group relative to the M-MSC. Moreover, the CCL2-MSC group displayed increased angiogenesis and endogenous neurogenesis, decreased neuro-inflammation but with increased healing-process inflammatory cells relative to other groups. These findings indicated that CCL2-overexpressing hUC-MSCs showed better functional recovery relative to na\u00efve hUC-MSCs according to the increased migration of these cells into brain areas of higher CCR2 expression, thereby promoting subsequent endogenous brain repair.<\/jats:p>","DOI":"10.3390\/ijms21207795","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T10:14:22Z","timestamp":1603275262000},"page":"7795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Enhancing the Therapeutic Potential of CCL2-Overexpressing Mesenchymal Stem Cells in Acute Stroke"],"prefix":"10.3390","volume":"21","author":[{"given":"Sanghun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7333-0647","authenticated-orcid":false,"given":"Ok Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kee Ook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeju","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0541-3528","authenticated-orcid":false,"given":"Nam Keun","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam 13488, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/ageing\/29.2.143","article-title":"Healthy ageing is associated with reduced and delayed disability","volume":"29","author":"Simons","year":"2000","journal-title":"Age Ageing"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"42","DOI":"10.5853\/jos.2018.03125","article-title":"Executive summary of stroke statistics in Korea 2018: A report from the epidemiology research council of the Korean stroke society","volume":"21","author":"Kim","year":"2019","journal-title":"J. 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