Human Mesenchymal Stem Cell-Derived Exosomes Promote the Proliferation and Melanogenesis of Primary Melanocytes by Attenuating the H2O2-Related Cytotoxicity in vitro

Background: Mesenchymal stem cell-derived exosomes (MSC-Exo) have therapeutic potential.However, the impact of MSC-Exo on the survival and melanogenesis of human primary melanocytes following H 2 O 2 -induced damage has not been clarified.We therefore investigated the effects of MSC-Exo on the H 2 O 2 -affected survival of human primary melanocytes and their proliferation, apoptosis, senescence, and melanogenesis in vitro.Methods: MSC-Exo were prepared from human MSCs by sequential centrifugations and characterized by Transmission Electron Microscopy, Western blot and Nanoparticle Tracking Analysis.Human primary melanocytes were isolated and treated with different concentrations of MSC-Exo, followed by exposing to H 2 O 2 .Furthermore, the impact of pretreatment with MSC-Exo on the proliferation, apoptosis, senescence and melanogenesis of melanocytes were tested by CCK-8, flow cytometry, Western blot, L-Dopa staining, tyrosinase activity and RT-qPCR.Results: Pretreatment with lower doses of MSC-Exo protected human primary melanocytes from the H 2 O 2 -triggered apoptosis, while pretreatment with higher doses of MSC-Exo enhanced the H 2 O 2 -induced melanocyte apoptosis.Compared with the untreated control, pretreatment with a lower dose (1 µg/mL) of MSC-Exo enhanced the proliferation of melanocytes, abrogated the H 2 O 2 -increased p53, p21, IL-1β, IL-6 and IL-8 expression and partially rescued the H 2 O 2 -decreased L-dopa staining reaction, tyrosinase activity, MITF and TRP1 expression in melanocytes. Conclusion:Our findings indicate that treatment with a low dose of MSC-Exo promotes the proliferation and melanogenesis of human primary melanocytes by ameliorating the H 2 O 2 -induced apoptosis and senescence of melanocytes.MSC-Exo may be a promising therapeutic strategy of vitiligo.