Abstract
BackgroundLarge 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.MethodsTo 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.ResultsIn 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.ConclusionThe 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.Graphical abstract
Highlights
Large numbers of adipose-derived stem cells (ADSCs) are obtained and have been demonstrated to protect against ultraviolet B (UVB)-induced skin photoaging
We have shown that ADSC-Extracellular vesicles (EVs) ameliorate UVBinduced skin photoaging in vivo and in vitro in a dosedependent manner
To explain the mechanism by which ADSC-EVs contribute to anti-photoaging, in vitro studies demonstrated that EVs improved FB activity, Fig. 5 Adipose-derived stem cell extracellular vesicles (ADSC-EVs) increased fibroblast (FB) activity and protected FBs from ultraviolet B (UVB)
Summary
Large numbers of adipose-derived stem cells (ADSCs) are obtained and have been demonstrated to protect against ultraviolet B (UVB)-induced skin photoaging. As a cell-free agent, adipose-derived stem cell extracellular vesicles (ADSC-EVs) have anti-photoaging potential. The topical application of antioxidants and growth factors has proven to be effective in preventing photoaging. Their usage has been limited by poor permeability and stability [2,3,4]. Adipose-derived stem cells (ADSCs) have been demonstrated to protect against ultraviolet B-induced skin photoaging [5,6,7], though there are concerns regarding tumorigenicity and risk of contamination from their production by cell culture [8]. Recent studies have demonstrated that the therapeutic effects of stem cells can be mainly attributed to paracrine mechanisms rather than their differentiation [9]
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