{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T23:27:43Z","timestamp":1772321263572,"version":"3.50.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>The beneficial effects of bone marrow mononuclear cell (BM-MNC) transplantation in preclinical experimental stroke have been reliably demonstrated. However, only overall modest effects in clinical trials were observed. We have investigated and reported a cause of the discrepancy between the preclinical and clinical studies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>To investigate the possible cause of low efficacy of BM-MNC transplantation in experimental stroke, we have focused on blood clot formation, which is not uncommon in human bone marrow aspirates. To evaluate the effects of clot-derived contaminants in transplanted BM-MNC on stroke outcome, a murine stroke model was used.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>We show that BM-MNC separated by an automatic cell isolator (Sepax2), which does not have the ability to remove clots, did not attenuate brain atrophy after stroke. In contrast, manually isolated, clot-free BM-MNC exerted therapeutic effects. Clot-derived contaminants were also transplanted intravenously to poststroke mice. We found that the transplanted contaminants were trapped at the peristroke area, which were associated with microglial\/macrophage activation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Clot-derived contaminants in transplanted BM-MNC nullify therapeutic effects in experimental stroke. This may explain neutral results in clinical trials, especially in those using automated stem cell separators that lack the ability to remove clot-derived contaminants.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Visual Overview\u2014<\/jats:title>\n            <jats:p>\n              An online\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"visual overview\">visual overview<\/jats:ext-link>\n              is available for this article.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.119.026669","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T09:00:32Z","timestamp":1568278832000},"page":"2883-2891","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Clot-Derived Contaminants in Transplanted Bone Marrow Mononuclear Cells Impair the Therapeutic Effect in 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A.T.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, Kobe, Japan (Y.O., A.K.-T., Y.T., Y.O., J.B., A.T.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Boltze","sequence":"additional","affiliation":[{"name":"From the Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, Kobe, Japan (Y.O., A.K.-T., Y.T., Y.O., J.B., A.T.)"},{"name":"School of Life Sciences, University of Warwick, United Kingdom (J.B.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheraz","family":"Gul","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Molecular Biology and Applied Ecology IME \u2013 ScreeningPort, Hamburg, Germany (S.G., 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