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CD34\u2009+\u2009cells were transfused into the ipsilateral brain infarct zone of cell-treated patients via the ICAA in the catheterization room.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The results demonstrated 100% safety and success rates for the procedure, and no long-term tumorigenesis was observed in cell-treated patients. In cell-treated patients, the angiogenesis capacity of circulating endothelial progenitor cells (EPCs)\/Matrigel was significantly greater after treatment than before treatment with granulocyte colony-stimulating factor (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Blood samples from the right internal jugular vein of the cell-treated patients presented significantly greater levels of the stromal cell-derived factor 1\u03b1\/EPC at 5, 10 and 30\u00a0min compared with 0\u00a0min (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.005). The National Institute of Health Stroke Scale scores were similar upon presentation, but a greater response was observed by Days 30 and 90 in the cell-treated group than in the control group. Tc-99\u00a0m brain perfusion was significantly greater at 180\u00a0days in the cell-treated group than in the control group (<jats:italic>p<\/jats:italic>\u2009=\u20090.046). The combined long-term end points (defined as death\/recurrent stroke\/or severe disability) were notably lower in the control group compared with the cell-treated group (14.3% vs. 50.0%, <jats:italic>p<\/jats:italic>\u2009=\u20090.103).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Intracarotid transfusion of autologous CD34\u2009+\u2009cells is safe and might improve long-term outcomes in patients with acute IS.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> ISRCTN, ISRCTN15677760. Registered 23 April 2018- Retrospectively registered, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/doi.org\/10.1186\/ISRCTN15677760\">https:\/\/doi.org\/10.1186\/ISRCTN15677760<\/jats:ext-link><\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-024-04021-7","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T09:57:37Z","timestamp":1732096657000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Long term outcomes of intracarotid arterial transfusion of circulatory-derived autologous CD34\u2009+\u2009cells for acute ischemic stroke patients\u2014A randomized, open-label, controlled phase II clinical trial"],"prefix":"10.1186","volume":"15","clinical-trial-number":[{"clinical-trial-number":"isrctn15677760","registry":"10.18810\/isrctn"}],"author":[{"given":"Hung-Sheng","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Hsun","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Hua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Che","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Y.","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Hung","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan-Yen","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheung-Fat","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6305-5717","authenticated-orcid":false,"given":"Hon-Kan","family":"Yip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"issue":"3","key":"4021_CR1","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1159\/000441098","volume":"45","author":"RV Krishnamurthi","year":"2015","unstructured":"Krishnamurthi RV, Moran AE, Feigin VL, Barker-Collo S, Norrving B, Mensah GA, Taylor S, Naghavi M, Forouzanfar MH, Nguyen G, Johnson CO. 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Intra-arterial infusion of autologous bone marrow mononuclear cells in patients with moderate to severe middle cerebral artery acute ischemic stroke. Cell Transplant. 2012;21(Suppl 1):S13-21.","journal-title":"Cell Transplant"},{"key":"4021_CR41","doi-asserted-by":"publisher","first-page":"45626","DOI":"10.18632\/oncotarget.17320","volume":"8","author":"FY Lee","year":"2017","unstructured":"Lee FY, Chen KH, Wallace CG, Sung PH, Sheu JJ, Chung SY, Chen YL, Lu HI, Ko SF, Sun CK, Chiang HJ, Chang HW, Lee MS, Yip HK. Xenogeneic human umbilical cord-derived mesenchymal stem cells reduce mortality in rats with acute respiratory distress syndrome complicated by sepsis. Oncotarget. 2017;8:45626\u201342.","journal-title":"Oncotarget"},{"key":"4021_CR42","first-page":"963689723119017","volume":"32","author":"KC Lin","year":"2023","unstructured":"Lin KC, Fang WF, Sung PH, Huang KT, Chiang JY, Chen YL, Huang CR, Li YC, Lee MS, Yip HK. Early and dose-dependent xenogeneic mesenchymal stem cell therapy improved outcomes in acute respiratory distress syndrome rodent through ameliorating inflammation. Oxid Stress, Immune React, Cell Transplant. 2023;32:9636897231190178.","journal-title":"Oxid Stress, Immune React, Cell Transplant"},{"key":"4021_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2023.100613","volume":"47","author":"CC Yang","year":"2024","unstructured":"Yang CC, Chen YL, Sung PH, Chiang JY, Chen CH, Li YC, Yip HK. Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat. Biomed J. 2024;47: 100613.","journal-title":"Biomed J"}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-024-04021-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-024-04021-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-024-04021-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T10:03:37Z","timestamp":1732097017000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-024-04021-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4021"],"URL":"https:\/\/doi.org\/10.1186\/s13287-024-04021-7","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]},"assertion":[{"value":"24 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This clinical trial protocol was reviewed and approved by the Taiwan Food and Drug Administration (Approval number: 1109012692) and the Institutional Review Board of Chang Gung Medical Foundation (Approval number: 201700116A0C502). This project entitled \u201cAn investigation of the therapeutic impact of intra-carotid arterial transfusion of autologous peripheral blood-derived stem cell\/progenitor cell (CD34\u2009+) therapy on brain ischemic stroke\u2014a phase II clinical trial\u201d was approved on July 17, 2017. Furthermore, all patients signed the approved informed consent form, and all the procedures were performed in accordance with the principles of the Declaration of Helsinki. Trial registration: ISRCTN, ISRCTN15677760. Registered 23 April 2018- Retrospectively registered, .","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"443"}}