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Drug treatments that reduce cellular senescence may enhance the regenerative capacity of BM\u2010MSCs. This study investigates the effects of losartan and fisetin, both separately and in combination, on cellular senescence and osteogenesis. Human BM\u2010MSCs were exposed to low and high concentrations of each drug for 24\u2009h. Our findings showed that high\u2010dose losartan exhibited cytotoxicity, focusing subsequent analyses on the low doses. Both low\u2010dose losartan and fisetin effectively mitigated cellular senescence, with combined treatment showing synergistic effects in reducing senescence markers. From these initial findings, subsequent experiments utilized low doses of both compounds to evaluate their effect on differentiation capacity. Our multimodal approach, incorporating flow cytometry, senescence\u2010associated heterochromatin foci (SAHF) immunohistochemistry, senescence\u2010associated secretory phenotype (SASP) quantification, and differentiation potential assays, revealed that the combination of 23.6\u2009\u03bcM of losartan and 50\u2009\u03bcM of fisetin was optimal for reducing cellular senescence and enhancing osteogenesis in BM\u2010MSCs. These results support potential therapeutic strategies to counteract age\u2010related declines in bone health and improve healing. By targeting cellular senescence while promoting osteogenesis, losartan and fisetin offer promising avenues for future research aimed at enhancing the regenerative capacity of BM\u2010MSCs in the context of musculoskeletal regenerative medicine.<\/jats:p>","DOI":"10.1155\/term\/9187855","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T14:29:42Z","timestamp":1742394582000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Combination Therapy of Losartan and Fisetin Reduces Senescence and Enhances Osteogenesis in Human Bone Marrow\u2013Derived Mesenchymal Stem Cells"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5070-1185","authenticated-orcid":false,"given":"Haruki","family":"Nishimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0110-1295","authenticated-orcid":false,"given":"Michael T.","family":"Mullen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-1390","authenticated-orcid":false,"given":"Kohei","family":"Yamaura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Huard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3379-0961","authenticated-orcid":false,"given":"Dane R. 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