ABSTRACT: BACKGROUND:Large numbers of adipose-derived stem cells (ADSCs) are easily obtained and have been demonstrated to protect against ultraviolet B (UVB)-induced skin photoaging. Extracellular vesicles (EVs) exhibit some of the same effects as the cells from which they originate and have many advantages over stem cells. In particular, their application circumvents many safety concerns associated with cell therapy. Thus, as a cell-free agent, adipose-derived stem cell extracellular vesicles (ADSC-EVs) have anti-photoaging potential. However, the protective effects of ADSC-EVs in skin photoaging remain uncertain. METHODS:To investigate the effect of ADSC-EVs on mice with UVB-induced photoaging, 150 ?g and 300 ?g ADSC-EVs were subcutaneously injected weekly into photoaging mice for 8? weeks. The protective effect was evaluated by gross assessment and hematoxylin and eosin, Masson's trichrome, and ?-galactosidase staining. Proliferating cell nuclear antigen, CD68, and dihydroethidium staining were performed to evaluate cell proliferation, inflammation infiltration, and reactive oxygen species (ROS) production, respectively. In vitro, 100 ?g/mL and 200 ?g/mL ADSC-EVs were used to treat photoaging fibroblasts (FBs). ?-galactosidase staining and collagen 1 and matrix metalloproteinase 3 (MMP-3) expression were analyzed to evaluate FB senescence. To explain the protective mechanism of ADSC-EVs, their role in regulating ROS production, antioxidant enzyme expression, cell cycle arrest, and inflammation was evaluated. RESULTS:In vivo, we showed that ADSC-EVs decreased skin wrinkles in mice with UVB-induced photoaging, while promoting epidermal cell proliferation and attenuating macrophage infiltration and ROS production. In vitro, we showed that ADSC-EVs increased FB activity and protected FBs from UVB-induced senescence, attenuated raw 264.7 cell differentiation from M0 to M1 macrophages, reduced intracellular ROS production, promoted antioxidant enzyme expression, and rescued FBs from cell cycle arrest. CONCLUSION:The anti-photoaging effect of ADSC-EVs was attributed to their ability to attenuate ROS production and the inflammatory response, which are key factors in MMP activation and collagen degradation.
