Anti-Inflammatory and Pro-Healing Effects of Human Plasma-Derived Exosomes in a Murine Wound Model.

BACKGROUND: Exosomes have emerged as key mediators in regenerative medicine because of their ability to facilitate intercellular signaling and promote tissue renewal. Exosomes from various origins have demonstrated efficacy in tissue regeneration. AIMS: To explore the potential of plasma-derived exosomes (PDEs) in wound healing through in vitro analyses and an in vivo mouse model. PATIENTS/METHODS: PDEs were isolated from blood and characterized using a nanoparticle assay. Human dermal fibroblasts (HDFs) were treated with PDEs at different concentrations to assess cell proliferation, migration, and gene expression. For in vivo evaluation, 8-mm full-thickness wounds were created on C57BL/6 mice and treated with either subcutaneous injection or topical smearing of PDEs at low (5 × 109/mL) or high (5 × 1010/mL) concentrations. Wound closure was monitored over an 8-day period, and tissue samples were collected for analysis. RESULTS: PDEs promoted HDF proliferation and migration in vitro, with significantly higher cell migration rates (38.2, 40.2%) compared to controls (17.8%, p < 0.001). Gene expression analysis revealed the upregulation of collagen synthesis markers (COL1A1) and the downregulation of degradation markers (MMP1). Both subcutaneous injection and topical smearing methods accelerated wound healing in vivo, with closure rates of 91.8%-96.5% in treated groups versus 70.9%-72.6% in controls by day 8. Treatment increased the expression of regenerative markers (Fgf1, Fn1) while reducing the levels of inflammatory markers (Il6, Ptgs2). CONCLUSION: PDEs promote wound healing by enhancing cell proliferation, stimulating collagen synthesis, and modulating inflammatory responses. Both subcutaneous injection and topical smearing were effective.