Mesenchymal Stem Cell Derived Exosomes Repair Uterine Injury by Targeting Transforming Growth Factor-β Signaling

Mesenchymal Stem Cell Derived Exosomes Repair Uterine Injury by Targeting Transforming Growth Factor-β SignalingClick to copy article linkArticle link copied! - Huidong LiuHuidong LiuDepartment of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100005, ChinaMore by Huidong Liu - Xiao ZhangXiao ZhangDepartment of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100005, ChinaMore by Xiao Zhang - Mengtong ZhangMengtong ZhangDepartment of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100005, ChinaMore by Mengtong Zhang - Sichen ZhangSichen ZhangDepartment of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100005, ChinaMore by Sichen Zhang - Jin LiJin LiThe Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100005, ChinaMore by Jin Li - Yingmin ZhangYingmin ZhangThe Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100005, ChinaMore by Yingmin Zhang - Qingyu WangQingyu WangThe Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100005, ChinaMore by Qingyu Wang - Jian Ping CaiJian Ping CaiThe Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100005, ChinaMore by Jian Ping Cai - Ke Cheng*Ke Cheng*Email: [email protected]Department of Biomedical Engineering, Columbia University, New York, New York 10032,United StatesMore by Ke Cheng - Shaowei Wang*Shaowei Wang*Email: [email protected]Department of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100005, ChinaMore by Shaowei Wang Abstract Intrauterine adhesions (IUA) refer to adhesions within the uterine cavity and cervix caused by injuries from uterine surgery. They are a significant cause of female infertility. Exosomes derived from mesenchymal stem cells (MSCs) play an active role in the treatment of IUA. However, the mechanism by which they reduce fibrosis in the damaged endometrium remains unclear. In this paper, we demonstrate that exosomes derived from placental mesenchymal stem cells (PMSCs) can restore uterine functions and improve the fertility rate of injured animals. This is achieved by promoting cell proliferation, increasing endometrial thickness, and reversing fibrosis. Regarding the molecular mechanism behind these therapeutic effects, we identify three specific miRNAs, namely, miR-125b-5p, miR-30c-5p, and miR-23a-3p, enriched in PMSC-exosomes, as the key players in the treatment of IUA. Specifically, miR-125b-5p/miR-30c-5p and miR-23a-3p inhibit the expression of smad2 and smad3 by targeting their 3′-untranslated regions, resulting in the downregulation of the transforming growth factor-β (TGF-β)/smad signaling pathway and the reversal of fibrosis. Notably, the safety of PMSC-exosomes in intrauterine treatment was also been confirmed. In conclusion, we illustrate that exosomes derived from PMSCs possess the capability to repair endometrial damage and enhance fertility in injured animals by regulating the TGF-β/smad pathway via miR-125b-5p, miR-30c-5p, and miR-23a-3p. This provides insights into the precision treatment of IUA through exosome-based cell-free therapy. Cited By This article is cited by 75 publications. - Li He, Hongrui Ji, Ju Huang, Jinxiao Yan, Shuoqi Tian, Shiyu Liu, Shizhe Chen, Yanwen Hao, Yuanchao Kang, Hui Yang, Ning Cui. 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