ArticleJournal of tissue engineering and regenerative medicine2025
Combination Therapy of Losartan and Fisetin Reduces Senescence and Enhances Osteogenesis in Human Bone Marrow-Derived Mesenchymal Stem Cells.
Article in Journal of tissue engineering and regenerative medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- A Review of Rejuvenation Strategies Targeting Mesenchymal Stem Cell Senescence and Their Impact on Bone Health and Regeneration.Current osteoporosis reports · 2026Review
- Mesenchymal Stromal Cell Rejuvenation Strategies to Enhance Clinical Translation in Cell Therapy.Aging cell · 2026Review
- Cellular senescence in musculoskeletal diseases: biological mechanisms and clinical implications.Theranostics · 2026Review
- Advances in 3D bioprinting for medical application: opportunities and challenges.Biomedical engineering online · 2025Review
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Authors and funding
11 authors.
Funding
Abstract
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 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-MSCs in the context of musculoskeletal regenerative medicine.
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Registered trials
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