Extracellular vesicles from adipose-derived stem cells ameliorate ultraviolet B-induced skin photoaging by attenuating reactive oxygen species production and inflammation

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 μg and 300 μg 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 β-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 μg/mL and 200 μg/mL ADSC-EVs were used to treat photoaging fibroblasts (FBs). β-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.

Microneedle based adipose derived stem cells‐derived extracellular vesicles therapy ameliorates UV‐induced photoaging in SKH‐1 mice

“…When the ADSCs‐EVs were injected into the UV‐induced photoaging mice weekly for 8 weeks, the wrinkles score was reduced significantly; a decrease in epidermal thickness and an increase in dermal thickness were also observed. In addition, the results supported that ADSCs‐EVs treatment was beneficial to collagen regeneration in vivo 27 …”

Applications of Mesenchymal Stem Cells in Skin Regeneration and Rejuvenation

“…Another way to use AD-MSCs in antiaging therapy, in a “cell-free” method of treatment, is by using extracellular vesicles (EVs), which have several advantages over stem cells and their safety issues. Adipose-derived mesenchymal stem cells extracellular vesicles (AD-MSCs-EVs) have anti-photoaging potential and were analyzed as subcutaneous injections in photoaged mice models [ 112 ]. The treatment resulted in a decrease in skin wrinkles and promotion of epidermal cell proliferation.…”

Chitosan Hydrogel-loaded MSC-derived Extracellular Vesicles Promote Skin Rejuvenation by Ameliorating the Senescence of Dermal Fibroblasts

“…UV light damage is one of the most harmful environmental factors that accelerate aging. Therefore, reports have suggested that EVs from adipose-derived stem cell have anti-photoaging potential (59,60). Together, these studies suggest that EVs from stem cell could be good candidates for therapeutic strategies against aging.…”