{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T03:49:24Z","timestamp":1778384964382,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T00:00:00Z","timestamp":1415232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Education, Science and Culture of Japan","award":["No.23390342 and No.25293305"],"award-info":[{"award-number":["No.23390342 and No.25293305"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Recently, both basic and clinical studies demonstrated that bone marrow stromal cell (<jats:styled-content style=\"fixed-case\">BMSC<\/jats:styled-content>) transplantation therapy can promote functional recovery of patients with<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>disorders. A non\u2010invasive method for cell tracking using<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>and superparamagnetic iron oxide (<jats:styled-content style=\"fixed-case\">SPIO<\/jats:styled-content>)\u2010based labeling agents has been applied to elucidate the behavior of transplanted cells. However, the long\u2010term safety of<jats:styled-content style=\"fixed-case\">SPIO<\/jats:styled-content>\u2010labeled<jats:styled-content style=\"fixed-case\">BMSC<\/jats:styled-content>s still remains unclear. The aim of this study was to investigate the short\u2010, middle\u2010 and long\u2010term safety of the<jats:styled-content style=\"fixed-case\">SPIO<\/jats:styled-content>\u2010labeled allogeneic<jats:styled-content style=\"fixed-case\">BMSC<\/jats:styled-content>transplantation. For this purpose,<jats:styled-content style=\"fixed-case\">BMSC<\/jats:styled-content>s were isolated from transgenic rats expressing green fluorescent protein (<jats:styled-content style=\"fixed-case\">GFP<\/jats:styled-content>) and were labeled with<jats:styled-content style=\"fixed-case\">SPIO<\/jats:styled-content>. The<jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>a\/<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>ATPase pump inhibitor ouabain or vehicle was stereotactically injected into the right striatum of wild\u2010type rats to induce a lacunar lesion (<jats:italic>n<\/jats:italic>\u2009=\u200922). Seven days after the insult, either<jats:styled-content style=\"fixed-case\">BMSC<\/jats:styled-content>s or<jats:styled-content style=\"fixed-case\">SPIO<\/jats:styled-content>solution were stereotactically injected into the left striatum. A 7.0\u2010Tesla<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>was performed to serially monitor the behavior of<jats:styled-content style=\"fixed-case\">BMSCs<\/jats:styled-content>in the host brain. The animals were sacrificed after 7 days (<jats:italic>n<\/jats:italic>\u2009=\u20097), 6 weeks (<jats:italic>n<\/jats:italic>\u2009=\u20096) or 10 months (<jats:italic>n<\/jats:italic>\u2009=\u20099) after the transplantation.<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>demonstrated that<jats:styled-content style=\"fixed-case\">BMSCs<\/jats:styled-content>migrated to the damage area through the corpus callosum. Histological analysis showed that activated microglia were present around the bolus of donor cells 7 days after the allogeneic cell transplantation, although an immunosuppressive drug was administered. The<jats:styled-content style=\"fixed-case\">SPIO<\/jats:styled-content>\u2010labeled<jats:styled-content style=\"fixed-case\">BMSCs<\/jats:styled-content>resided and started to proliferate around the route of the cell transplantation. Within 6 weeks, large numbers of<jats:styled-content style=\"fixed-case\">SPIO<\/jats:styled-content>\u2010labeled<jats:styled-content style=\"fixed-case\">BMSCs<\/jats:styled-content>reached the lacunar infarction area from the transplantation region through the corpus callosum. Some<jats:styled-content style=\"fixed-case\">SPIO<\/jats:styled-content>nanoparticles were phagocytized by microglia. After 10 months, the number of<jats:styled-content style=\"fixed-case\">SPIO<\/jats:styled-content>\u2010positive cells was lower compared with the 7\u2010day and 6\u2010week groups. There was no tumorigenesis or severe injury observed in any of the animals. These findings suggest that<jats:styled-content style=\"fixed-case\">BMSC<\/jats:styled-content>s are safe after cell transplantation for the treatment of stroke.<\/jats:p>","DOI":"10.1111\/neup.12180","type":"journal-article","created":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T03:20:18Z","timestamp":1415330418000},"page":"197-208","source":"Crossref","is-referenced-by-count":15,"title":["Short\u2010, middle\u2010 and long\u2010term safety of superparamagnetic iron oxide\u2010labeled allogeneic bone marrow stromal cell transplantation in rat model of lacunar infarction"],"prefix":"10.1111","volume":"35","author":[{"given":"Chengbo","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Hokkaido University Graduate School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Shichinohe","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Hokkaido University Graduate 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