{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:08:51Z","timestamp":1792267731053,"version":"4.4.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":716,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T00:00:00Z","timestamp":1574035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T00:00:00Z","timestamp":1574035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The present study used in vitro and in vivo stroke models to demonstrate the safety, efficacy, and mechanism of action of adult human bone marrow-derived NCS-01 cells. Coculture with NCS-01 cells protected primary rat cortical cells or human neural progenitor cells from oxygen glucose deprivation. Adult rats that were subjected to middle cerebral artery occlusion, transiently or permanently, and subsequently received intracarotid artery or intravenous transplants of NCS-01 cells displayed dose-dependent improvements in motor and neurological behaviors, and reductions in infarct area and peri-infarct cell loss, much better than intravenous administration. The optimal dose was 7.5\u2009\u00d7\u2009106 cells\/mL when delivered via the intracarotid artery within 3\u2009days poststroke, although therapeutic effects persisted even when administered at 1 week after stroke. Compared with other mesenchymal stem cells, NCS-01 cells ameliorated both the structural and functional deficits after stroke through a broad therapeutic window. NCS-01 cells secreted therapeutic molecules, such as basic fibroblast growth factor and interleukin-6, but equally importantly we observed for the first time the formation of filopodia by NCS-01 cells under stroke conditions, characterized by cadherin-positive processes extending from the stem cells toward the ischemic cells. Collectively, the present efficacy readouts and the novel filopodia-mediated mechanism of action provide solid lab-to-clinic evidence supporting the use of NCS-01 cells for treatment of stroke in the clinical setting.<\/jats:p><jats:sec><jats:title\/><jats:p>Significance statement The present study recognizes critical translational gaps in stem cell transplant dose, route, and timing after stroke, and acknowledges solid safety profile of mesenchymal stem cells. The study tested a human bone marrow-derived mesenchymal stem cell line called NCS-01 in oxygen glucose deprivation and middle cerebral artery occlusion models, which revealed the optimal dose of 7.5\u2009\u00d7\u2009106 cells\/mL via the intracarotid artery within 3\u2009days poststroke. Secretion of cytokines, specifically bFGF and IL-6, and filopodia formation, are potential mechanisms. Based on these preclinical data, the FDA in July 2019 approved intracarotid NCS-01 cell transplantation in ischemic stroke patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/sctm.19-0229","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T10:33:00Z","timestamp":1574073180000},"page":"203-220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Translating intracarotid artery transplantation of bone marrow-derived NCS-01 cells for ischemic stroke: Behavioral and histological readouts and mechanistic insights into stem cell therapy"],"prefix":"10.1093","volume":"9","author":[{"given":"Yuji","family":"Kaneko","sequence":"first","affiliation":[{"name":"1 Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair University of South Florida College of Medicine, Tampa, 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