Zeng Qianwen, Yu Rentao, Bai Genlong, Wu Qian, Chen Bo, Chen Aijun
Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Key Laboratory of Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing, China.
Photochem Photobiol. 2025 Jul 30. doi: 10.1111/php.70015.
Skin photoaging is a skin condition caused by long-term exposure to ultraviolet radiation, especially UVA and UVB, which leads to wrinkles, pigmentation, skin sagging, and telangiectasia. Histopathologically, it is characterized by a significant reduction in dermal collagen and abnormal accumulation of elastic fibers. Preventing or ameliorating photoaging may provide a promising therapeutic approach for these changes. In recent years, multiple studies have reported the potential of mesenchymal stem cells (MSCs) in treating various skin diseases. Given that extracellular vesicles (EVs) can deliver diverse substances to receptor cells and produce therapeutic effects similar to parental cells, we aim to explore whether adipose-derived mesenchymal stem cell-derived extracellular vesicles (AMSC-EVs) can improve skin photoaging by delivering heat shock protein 27 (HSP27). The specific effects of AMSC-EVs on the photoaging model of human dermal fibroblasts (HDFs) or human immortalized keratinocytes (HaCaTs) induced by UVB irradiation were investigated through CCK-8 experiments, cell migration experiments, flow cytometry, immunofluorescence, and Western blot. Our research found that AMSC-EVs improved the survival rate and migration ability of HDFs and HaCaTs after UVB irradiation, alleviated cell senescence, reduced DNA damage, inhibited the production of ROS, and promoted the remodeling of extracellular matrix (ECM). Further research showed that after knocking down HSP27, the anti-aging/light protection ability of AMSC-EVs was significantly weakened. Overall, our data suggest that we have revealed the anti-photoaging effect of AMSC-EVs on HDFs and HaCaTs, which may be mediated by the delivery of HSP27.
皮肤光老化是一种由于长期暴露于紫外线辐射，尤其是UVA和UVB而导致的皮肤状况，会引发皱纹、色素沉着、皮肤松弛和毛细血管扩张。在组织病理学上，其特征是真皮胶原蛋白显著减少以及弹性纤维异常积聚。预防或改善光老化可能为这些变化提供一种有前景的治疗方法。近年来，多项研究报道了间充质干细胞（MSCs）在治疗各种皮肤疾病方面的潜力。鉴于细胞外囊泡（EVs）可以将多种物质传递给受体细胞并产生与亲代细胞相似的治疗效果，我们旨在探索脂肪来源的间充质干细胞衍生的细胞外囊泡（AMSC-EVs）是否可以通过递送热休克蛋白27（HSP27）来改善皮肤光老化。通过CCK-8实验、细胞迁移实验、流式细胞术、免疫荧光和蛋白质免疫印迹法研究了AMSC-EVs对紫外线B（UVB）照射诱导的人皮肤成纤维细胞（HDFs）或人永生化角质形成细胞（HaCaTs）光老化模型的具体影响。我们的研究发现，AMSC-EVs提高了UVB照射后HDFs和HaCaTs的存活率和迁移能力，减轻了细胞衰老，减少了DNA损伤，抑制了活性氧（ROS）的产生，并促进了细胞外基质（ECM）的重塑。进一步的研究表明，敲低HSP27后，AMSC-EVs的抗老化/光保护能力显著减弱。总体而言，我们的数据表明，我们揭示了AMSC-EVs对HDFs和HaCaTs的抗光老化作用，这可能是由HSP27的递送介导的。
