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Young fibroblast-derived exosomal microRNA-125b transfers beneficial effects on aged cutaneous wound healing

Wenzheng Xia1, Minxiong Li1, Xingyu Jiang2

  • 1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.

Journal of Nanobiotechnology
|March 20, 2022
PubMed

Insights

Young fibroblast exosomes containing miR-125b promote wound healing in aged mice by enhancing myofibroblast differentiation and migration, offering a potential anti-aging strategy.

Area of Science:

  • Regenerative Medicine
  • Aging Biology
  • Wound Healing Research

Background:

  • Aged skin exhibits impaired wound healing due to reduced myofibroblasts and defective extracellular matrix (ECM) deposition.
  • Cell-cell communication via exosome-borne microRNAs (miRs) is crucial for tissue regeneration and wound repair.
  • Age-related fibroblast dysfunction at wound edges hinders effective healing.

Purpose of the Study:

  • To investigate the potential of exosomes from young fibroblasts to improve wound healing in aged mice.
  • To elucidate the molecular mechanisms underlying exosome-mediated enhancement of fibroblast function and wound repair.

Main Methods:

  • Comparison of aged and young fibroblasts' migration, differentiation, and ECM deposition.
  • Administration of exosomes derived from young mouse wound-edge fibroblasts (exosomesYoung) to aged mice wounds.
  • In vitro assessment of fibroblast behavior upon exosome treatment.
  • Analysis of microRNA-125b (miR-125b) and Sirtuin 7 (Sirt7) roles in exosome-mediated effects.

Main Results:

  • ExosomesYoung significantly enhanced myofibroblast abundance and accelerated wound healing in aged mice.
  • ExosomesYoung promoted fibroblast migration and myofibroblast transition in vitro.
  • Exosomal transfer of miR-125b inhibited Sirt7 in aged fibroblasts, driving differentiation and healing.
  • Inhibition of miR-125b or overexpression of Sirt7 impaired fibroblast migration and transition.

Conclusions:

  • Exosomes from young fibroblasts, carrying miR-125b, can counteract age-related wound healing deficits.
  • miR-125b transfer via exosomes promotes fibroblast migration and myofibroblast differentiation by inhibiting Sirt7.
  • This exosome-guided mechanism presents a promising therapeutic strategy for anti-aging interventions in wound healing.
Keywords:
ECM depositionExosome induced microRNA deliveryFibroblast to myofibroblast transitionSenescenceWound healing

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