Biologically Distinct, Clinically Convergent: A Comparative Study of Umbilical Cord- and Adipose-Derived Mesenchymal Stem Cell Exosomes in Human Skin Regeneration.

Mesenchymal stem cell (MSC)-derived exosomes are emerging as cell-free bioregenerative platforms in aesthetic dermatology. Umbilical cord (UC-MSC) and adipose-derived (AD-MSC) exosomes are among the most studied sources, yet existing data derive from heterogeneous models that preclude direct comparison. No standardized head-to-head evaluation in a human skin aging model has been conducted. The aim of the study is to compare the regenerative and antiaging effects of UC-MSC and AD-MSC exosomes using a physiologically relevant ex vivo human skin aging model. MSCs were isolated and characterized per International Society for Cellular Therapy criteria. Exosomes were purified through differential ultracentrifugation and analyzed by nanoparticle tracking and flow cytometry. Cytokine cargo was profiled using multiplex assays. Human dermal fibroblasts and ex vivo skin explants were used to assess proliferation, senescence-associated β-gal activity, melanogenesis, senescence-associated secretory phenotype (SASP) suppression (interleukin-6, matrix metalloproteinase-9), and extracellular matrix (ECM) biosynthesis. Topical retinoic acid and resveratrol served as reference controls. Both exosome types increased fibroblast proliferation and reduced senescence. AD-MSC exosomes showed higher vascular endothelial growth factor (VEGF) content, driving angiogenesis and greater collagen and hyaluronic acid production. UC-MSC exosomes, enriched in transforming growth factor-beta and platelet-derived growth factor-BB (PDGF-BB), demonstrated stronger immunomodulatory activity and more pronounced SASP reduction in ultraviolet-damaged skin. Both reduced melanogenesis without altering melanocyte viability. UC-MSC and AD-MSC exosomes exhibit distinct yet complementary regenerative profiles. AD-MSC exosomes favor dermal ECM remodeling and hydration, whereas UC-MSC exosomes exert potent anti-inflammatory and photo-protective effects. These findings support their potential for personalized regenerative dermatology and combinatory exosome-based facial rejuvenation strategies.