Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Department of Cell Biology, School of Life Sciences, Shanghai University, Shanghai, China.
Signal Transduct Target Ther. 2024 Oct 30;9(1):294. doi: 10.1038/s41392-024-01993-z.
UVB radiation induces oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, compromised barrier function, and an increased risk of carcinogenesis. Addressing or preventing photoaging may offer a promising therapeutic avenue for these conditions. Recent research indicated that mesenchymal stem cells (MSCs) exhibit significant therapeutic potential for various skin diseases. Given that extracellular vesicles (EV) can deliver diverse cargo to recipient cells and elicit similar therapeutic effects, we investigated the roles and underlying mechanisms of both adipose-derived MSC-derived EV (AMSC-EV) and umbilical cord-derived MSC-derived EV (HUMSC-EV) in photoaging. Our findings indicated that in vivo, treatment with AMSC-EV and HUMSC-EV resulted in improvements in wrinkles and skin hydration while also mitigating skin inflammation and thickness alterations in both the epidermis and dermis. Additionally, in vitro studies using human keratinocytes (HaCaTs), human dermal fibroblast cells (HDFs), and T-Skin models revealed that AMSC-EV and HUMSC-EV attenuated senescence, reduced levels of reactive oxygen species (ROS) and DNA damage, and alleviated inflammation induced by UVB. Furthermore, EV treatment enhanced cell viability and migration capacity in the epidermis and promoted extracellular matrix (ECM) remodeling in the dermis in photoaged cell models. Mechanistically, proteomics results showed that TIMP1 was highly expressed in both AMSC-EV and HUMSC-EV and could exert similar effects as MSC-EV. In addition, we found that EV and TIMP1 could inhibit Notch1 and downstream targets Hes1, P16, P21, and P53. Collectively, our data suggests that both AMSC-EV and HUMSC-EV attenuate skin photoaging through TIMP1/Notch1.
UVB 辐射会导致氧化应激、DNA 损伤和炎症，从而导致皮肤皱纹、屏障功能受损，并增加致癌风险。解决或预防光老化可能为这些疾病提供有前途的治疗途径。最近的研究表明，间充质干细胞（MSCs）对各种皮肤疾病具有显著的治疗潜力。鉴于细胞外囊泡（EV）可以向受体细胞传递多种货物并产生类似的治疗效果，我们研究了脂肪来源的 MSC 衍生 EV（AMSC-EV）和脐带来源的 MSC 衍生 EV（HUMSC-EV）在光老化中的作用和潜在机制。我们的研究结果表明，在体内，用 AMSC-EV 和 HUMSC-EV 治疗可改善皱纹和皮肤水分，同时减轻表皮和真皮的皮肤炎症和厚度改变。此外，使用人角质形成细胞（HaCaTs）、人真皮成纤维细胞（HDFs）和 T-Skin 模型进行的体外研究表明，AMSC-EV 和 HUMSC-EV 可减轻衰老、降低活性氧（ROS）和 DNA 损伤水平，并缓解 UVB 诱导的炎症。此外，EV 处理可增强光老化细胞模型中表皮的细胞活力和迁移能力，并促进真皮中的细胞外基质（ECM）重塑。在机制上，蛋白质组学结果表明 TIMP1 在 AMSC-EV 和 HUMSC-EV 中均高度表达，并且可以发挥与 MSC-EV 相似的作用。此外，我们发现 EV 和 TIMP1 可以抑制 Notch1 和下游靶标 Hes1、P16、P21 和 P53。总之，我们的数据表明，AMSC-EV 和 HUMSC-EV 通过 TIMP1/Notch1 减轻皮肤光老化。
