Human Placental Mesenchymal Stem Cell-Derived Exosomes in Wound Healing and Scar Therapy: A Systematic Review and Meta-analysis

Exosome therapy represents an emerging regenerative medicine approach for optimizing wound healing and reducing scarring. Extensive pre-clinical research on human placental mesenchymal stem cell-derived exosomes (hpMSC-exosomes) demonstrates significant therapeutic potential in aesthetic and reconstructive surgery applications. Despite compelling preclinical evidence supporting the efficacy of exosomes in wound healing, human clinical studies remain scarce. The author's current study includes 738 patients treated with hpMSC-exosomes over a 7-year period across multiple aesthetic and reconstructive indications, with 175 cases involving wound healing and 118 cases involving scar therapy. The objective of this systematic review and meta-analysis is to comprehensively evaluate the current evidence for hpMSC-exosomes in wound healing and scar therapy, analyzing their mechanisms of action, clinical applications, and safety profiles through a review of preclinical studies, safety data, and clinical case series in both animals and humans. Analysis of the author's series will be included. Information sources included PubMed, Cochrane Library, EMBASE, Web of Science, and ClinicalTrials.gov resulting in a meta-analysis of 21 global preclinical studies (323 animals) which demonstrated superior outcomes compared with controls across multiple parameters: wound healing rate, neovascular density, re-epithelialization rate, and collagen deposition. hpMSC-exosomes demonstrated accelerated wound healing through enhanced angiogenesis, reduced inflammation, improved collagen production, and immunomodulatory effects. Most studies utilized rodent models, with limited translation to human trials. Current human evidence is predominantly based on early-phase trials, case series, and observational studies. Large-scale, well-designed clinical trials are essential to advancing exosome therapy in wound healing and scar management. hp-MSC-exosomes represent a promising therapeutic modality for wound healing and scar therapy with demonstrated safety and efficacy. Standardization of manufacturing processes and FDA approval remain critical for widespread clinical implementation. Level of Evidence: 3 (Therapeutic).