The Efficacy And Mechanism Of Microneedle Combined With Extracellular Vesicles Secreted By Adipocyte-derived Stem Cells Prevent The UV-induced Photoaging In SKH-1 Mice Model

BackgroundSkin photoaging is exogenous skin aging caused by long-term ultraviolet(UV)exposure.UV can stimulate skin cells to produce a large number of oxidative stress responses,directly and indirectly induce DNA mutations and change gene expression patterns,cause changes in skin tissue structure and tissue microenvironment,and reduce physiological functions such as barrier functions and immune surveillance.In recent years,mesenchymal stem cells and their extracellular vesicles(EVs)-related therapies have received widespread attention in the fields of skin aging and damage repair.EVs are tiny vesicles secreted by a variety of cells.As an important intercellular signal transmission tool,they can regulate the physiological activities of recipient cells.Previous studies have shown that the culture supernatant of mesenchymal stem cells can improve the photoaging performance of mouse models,but the effective components in the culture supernatant are still unclear;the source of human adipose-derived stem cells(ADSCs)EVs can effectively improve UV-induced damage to human fibroblasts and keratinocytes,but their in vivo effects have not been proven.In this study,extracellular vesicles of human adipose-derived mesenchymal stem cells were extracted,and topical EVs combined with microneedles were used to study the delayed and repair effects and mechanisms of UV-induced SKH-1 hairless mice.ObjectiveTo study the therapeutic effect of microneedle combined with extracellular vesicles(EVs)secreted by adipocyte-derived stem cells on a UV-induced photoaging mice model.MethodsThe UV-induced photoaging mice were randomly divided into three groups,the control group,the microneedle group and the microneedle combined with EVs group.The photoaging grading scale and the photo damage grading scale were applied to evaluate the physical appearance of mice,the trans-epidermal water loss(TEWL)and the skin hydration were detected to assess the skin barrier function of mice;the structure of skin,the collagen fibers and the elastic fibers were evaluated histopathologically,and RT-PCR was used to detected the expression level of MMPs and Filaggrin in different groups.ResultsCompared with the control group,the severity of photodamage,the TEWL and the epidermal thickness were significantly reduced in the microneedle combined with EVs group,and the percentage of collagen area in dermis was significantly increased.The MMP-12 expression in the microneedle combined with EVs group was down-regulated slightly compared to the control group,and the expression of Filaggrin was slightly up-regulated.Conclusionmicroneedle combined with EVs can attenuate the UV-induced photoaging in SKH-1 mice model,and the mechanism is probably related to the reduce of collagen degradation and the improvement of skin barrier function.