{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T10:59:59Z","timestamp":1793012399868,"version":"4.5.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Multilineage-differentiating stress-enduring cells are endogenous nontumorigenic reparative pluripotent-like stem cells found in bone marrow, peripheral blood, and connective tissues. Topically administered human multilineage-differentiating stress-enduring cells into rat\/mouse stroke models differentiated into neural cells and promoted clinically relevant functional recovery. However, critical questions on the appropriate timing and dose, and safety of the less invasive intravenous administration of clinical-grade multilineage-differentiating stress-enduring cell\u2013based product CL2020 remain unanswered.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>\n              Using an immunodeficient mouse lacunar model, CL2020 was administered via the cervical vein in different doses (high dose=5\u00d710\n              <jats:sup>4<\/jats:sup>\n              cells\/body; medium dose=1\u00d710\n              <jats:sup>4<\/jats:sup>\n              cells\/body; low dose=5\u00d710\n              <jats:sup>3<\/jats:sup>\n              cells\/body) at subacute phase (\u22489 days after onset) and chronic phase (\u224830 days). Cylinder test, depletion of human cells by diphtheria toxin administration, immunohistochemistry, and human specific-genome detection were performed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>Tumorigenesis and adverse effects were not detected for up to 22 weeks. The high-dose group displayed significant functional recovery compared with the vehicle group in cylinder test in subacute-phase\u2013treated and chronic-phase\u2013treated animals after 6 weeks and 8 weeks post-injection, respectively. In the high-dose group of subacute-phase\u2013treated animals, robust and stable recovery in cylinder test persisted up to 22 weeks compared with the vehicle group. In both groups, intraperitoneal injection of diphtheria toxin abrogated the functional recovery. Anti-human mitochondria revealed CL2020 distributed mainly in the peri-infarct area at 1, 10, and 22 weeks and expressed NeuN (neuronal nuclei)- and MAP-2 (microtubule-associated protein-2)-immunoreactivity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Intravenously administered CL2020 was safe, migrated to the peri-infarct area, and afforded functional recovery in experimental stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.119.026589","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T10:00:26Z","timestamp":1576144826000},"page":"601-611","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":58,"title":["Intravenously Transplanted Human Multilineage-Differentiating Stress-Enduring Cells Afford Brain Repair in a Mouse Lacunar Stroke Model"],"prefix":"10.1161","volume":"51","author":[{"given":"Takatsugu","family":"Abe","sequence":"first","affiliation":[{"name":"From the Department of Neurosurgery (T.A., D.A., K.N., N.I., T.K., T.T.), Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Aburakawa","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (T.A., D.A., K.N., N.I., T.K., T.T.), Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniyasu","family":"Niizuma","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (T.A., D.A., K.N., N.I., T.K., T.T.), Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"},{"name":"Department of Neurosurgical Engineering and Translational Neuroscience (K.N.), Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"},{"name":"Department of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Miyagi, Japan (K.N.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Iwabuchi","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (T.A., D.A., K.N., N.I., T.K., T.T.), Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Kajitani","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (T.A., D.A., K.N., N.I., T.K., T.T.), Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Wakao","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Histology (S.W., Y.K., M.D.), Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Kushida","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Histology (S.W., Y.K., M.D.), Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Dezawa","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Histology (S.W., Y.K., M.D.), Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar V.","family":"Borlongan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa (C.V.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teiji","family":"Tominaga","sequence":"additional","affiliation":[{"name":"From the Department of 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