Human adipose and umbilical cord mesenchymal stem cellderived extracellular vesicles mitigate photoaging via TIMP1/Notch1  

作　　者：Huan Zhang Xian Xiao Liping Wang Xianhao Shi Nan Fu Shihua Wang Robert Chunhua Zhao 

机构地区：[1]Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing,China [2]Department of Cell Biology,School of Life Sciences,Shanghai University,Shanghai,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第11期5319-5335,共17页信号转导与靶向治疗（英文）

基　　金：supported by the CAMS Initiative for Innovative Medicine(2022-I2M-1-012);the 111 Project(B18007);National Key R&D Program of China(2020YFA0113000);Key-Area Research and Development Program of Guangdong Province(2021B0909060001);2021 General Research Institute for Nonferrous Metals‘Unveiling and Commanding’Project(2021JC0103).

摘　　要：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.

关 键 词：NOTCH1 INFLAMMATION alterations 

分 类 号：R392.2[医药卫生—免疫学]