{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:08:18Z","timestamp":1787098098718,"version":"build-2736575974"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP20K08636"],"award-info":[{"award-number":["JP20K08636"]}]},{"name":"JSPS KAKENHI","award":["JP23K07719"],"award-info":[{"award-number":["JP23K07719"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23bk0104124"],"award-info":[{"award-number":["JP23bk0104124"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Preemptive regenerative medicine using mesenchymal stem cells (MSCs) may provide a novel therapeutic approach to prevent the progression from organ damage to organ failure. Although immunosuppressive drugs are often used in patients with organ disorder, their impact on MSC therapy remains unclear. We investigated the effects of immunosuppressive drugs on the therapeutic efficacy of MSCs. We created unilateral ureteral obstruction models, as a well-established model of renal fibrosis, a preliminary stage of organ failure. Three immunosuppressive drugs (methylprednisolone, cyclosporine, and cyclophosphamide) were intraperitoneally administered 3 days after surgery, and MSCs were injected via tail vein the following day. Preadministration of methylprednisolone or cyclophosphamide interfered with MSC activation by reducing expression of interferon-gamma (IFN-\u03b3) and high-mobility group box-1 protein, thus significantly attenuating the therapeutic efficacy of MSCs. Preadministration of cyclophosphamide downregulated the expression of stromal cell-derived factor-1\/C-X-C motif ligand 12, which is a potent migration factor for MSCs, resulting in reduced MSC engraftment in the renal cortex. IFN-\u03b3-preconditioned activated MSCs were unaffected by these drugs and maintained their beneficial therapeutic effects. Cyclosporine preadministration had no effect on the therapeutic efficacy of MSCs. Our study demonstrated that the administration of certain immunosuppressive drugs interfered with MSC activation and engraftment at the site of injury, resulting in a significant attenuation of their therapeutic efficacy. These findings provide crucial information for selecting patients suitable for MSC therapy. Use of MSCs preactivated with IFN-\u03b3 or other means is preferred for patients on methylprednisolone or cyclophosphamide.<\/jats:p>","DOI":"10.1093\/stcltm\/szae073","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T18:34:36Z","timestamp":1728930876000},"page":"1067-1085","source":"Crossref","is-referenced-by-count":2,"title":["Impact of immunosuppressive drugs on efficacy of mesenchymal stem cell therapy for suppressing renal fibrosis"],"prefix":"10.1093","volume":"13","author":[{"given":"Kisho","family":"Miyasako","sequence":"first","affiliation":[{"name":"Department of Nephrology, Hiroshima University Hospital , 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-1494","authenticated-orcid":false,"given":"Ayumu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Hiroshima University Department of Stem Cell Biology and Medicine, Graduate School of Biomedical and Health Sciences, , 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima , ,\u00a0","place":["Japan"]},{"name":"University of Yamanashi Department of Nephrology, Graduate School of Medicine, , 1110 Shimokato, Chuo, Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ishiuchi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hiroshima University Hospital , 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima ,","place":["Japan"]},{"name":"Department of Stem Cell Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University , 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hiroshima University Hospital , 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 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