Combination Therapy of Losartan and Fisetin Reduces Senescence and Enhances Osteogenesis in Human Bone Marrow-Derived Mesenchymal Stem Cells
Nishimura H., Murata Y., Mullen MT., Yamaura K., Singer J., Huard C.
Laboratory Study, published in J Tissue Eng Regen Med (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Laboratory Study
- Journal
- J Tissue Eng Regen Med (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 40224958
- PMCID
- PMC11944977
- DOI
- 10.1155/term/9187855
- Citations
- 2
Abstract (original English)
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are well established for their osteogenic potential but are prone to senescence with aging or in vitro expansion. Drug treatments that reduce cellular senescence may enhance the regenerative capacity of BM-MSCs. This study investigates the effects of losartan and fisetin, both separately and in combination, on cellular senescence and osteogenesis. Human BM-MSCs were exposed to low and high concentrations of each drug for 24 h. Our findings showed that high-dose losartan exhibited cytotoxicity, focusing subsequent analyses on the low doses. Both low-dose 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-associated heterochromatin foci (SAHF) immunohistochemistry, senescence-associated secretory phenotype (SASP) quantification, and differentiation potential assays, revealed that the combination of 23.6 μM of losartan and 50 μM of fisetin was optimal for reducing cellular senescence and enhancing osteogenesis in BM-MSCs. These results support potential therapeutic strategies to counteract age-related declines in bone health and
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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