Exosomes derived from galangin preconditioned mesenchymal stem cells attenuate oxidative stress induced senescence and promote geriatric wound healing
- Sci Rep. 2026 Apr 30;16(1):20077. doi: 10.1038/s41598-026-50218-6.
- 1. Department of Dermatology, Taipei City Hospital, Zhongxing Branch, Taipei, Taiwan, ROC.
- 2. Department of Cosmetic Applications and Management, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan, ROC.
- 3. Department of Health and Welfare, University of Taipei, Taipei, Taiwan, ROC.
- 4. Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan, ROC.
- 5. Department of Orthopedic Surgery, Chung-Shan Medical University Hospital, Taichung, Taiwan, ROC.
- 6. School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
- 7. Center for Molecular Medicine in Traditional Chinese Medicine, E-Da Hospital, E-Da Healthcare Group, Kaohsiung, Taiwan.
- 8. School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan.
- 9. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
- 10. Department of Biotechnology, Asia University, Taichung, Taiwan.
- 11. Graduate Institute of Biomedical Science, China Medical University, Taichung City, Taiwan.
- 12. Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
- 13. Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan, ROC. [email protected].
- 14. School of Pharmacy, China Medical University, Taichung, Taiwan, ROC. [email protected].
- # Contributed equally.
Skin repair capacity decreases with age due to the accumulation of dermal cells with a senescence-associated secretory phenotype (SASP) and ensuing microenvironmental dysfunction. Mesenchymal stem cells (MSCs) release exosomes with demonstrated cytoprotective properties, suggesting that targeted delivery of exosomes from therapeutically primed MSCs could be an effective strategy to restore geriatric skin healing capacity. This study investigated the therapeutic potential of exosomes from MSCs pretreated with the natural flavonoid galangin (Gal-Exos) for mitigating dermal fibroblast senescence and enhancing aged skin repair. Wharton’s jelly-derived (WJ)MSCs were preconditioned with galangin and then seeded in transwell coculture with H₂O₂-induced senescent human dermal fibroblasts (HDFs). Additionally, HDFs were treated directly with control Exos or Gal-Exos. A galactose-induced mouse model of skin aging was established to assess Gal-Exo effects on experimental wound healing. Galangin preconditioning enhanced WJMSC proliferative capacity while preserving stemness as evidenced by elevated OCT4 and Nanog expression, and mitigated WJMSC senescence as indicated by reduced p21 and p53 expression. Transwell coculture with preconditioned WJMSCs elevated Collagen I/III synthesis, reduced senescence marker expression, and suppressed matrix metalloprotease (MMP)-1 and MMP-3 production by HDFs. Gal-Exos physically resembled control Exos but exhibited a “youth-associated” miRNA profile. Direct Gal-Exos administration rescued HDF senescence and accelerated wound closure in the mouse model concomitant with enhanced angiogenesis (indicated by CD31 upregulation), myofibroblast activation (evidenced by α-SMA upregulation), and Collagen deposition as well as with SASP reversal. Exosomes from galangin-treated WJMSCs may help restore the reparative capacity of aged skin by modulating SASP dynamics and extracellular matrix remodeling.
Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-50218-6.
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Research Areas: Cancer