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Melatonin-Primed MSCs Alleviate Intrauterine Adhesions by Affecting MSC-Expressed Galectin-3 on Macrophage Polarization

间充质干细胞 巨噬细胞极化 M2巨噬细胞 褪黑素 生物 干细胞 男科 巨噬细胞 癌症研究 免疫学 内分泌学 医学 细胞生物学 体外 生物化学
作者
Qi Jiang,Jingman Li,Yuchen Pan,Jiali Wang,Jingjing Yang,Sunan Shen,Yayi Hou
出处
期刊:Stem Cells [Wiley]
卷期号:40 (10): 919-931 被引量:7
标识
DOI:10.1093/stmcls/sxac049
摘要

Abstract Intrauterine adhesion (IUA) is characterized by the presence of fibrosis in the uterine cavity. It is mainly caused by infection or trauma to the endometrium, and it imposes a great challenge to female reproductive health. Mesenchymal stem cells (MSCs) have been used to regenerate the human endometrium in patients with IUA, but stem cell therapy is not curative in some patients. Melatonin (MT) was reported as a potential modulator of MSCs. However, it remains unclear whether MSCs pretreated with MT exert an improved therapeutic effect on IUA. In this study, an IUA model was established using our invented electric scratching tool. Our results illustrated that MT-pretreated MSCs significantly attenuated the development of IUA. Moreover, MT-pretreated MSCs highly expressed galectin-3 (Gal-3), which enhanced MSC proliferation and migration and influenced macrophage polarization. Of note, IUA mice exhibited colonic injury, and MT-pretreated MSCs alleviated this injury by normalizing colonic microbial communities and recruiting macrophages. Furthermore, inhibition of sympathetic nerves had no effect on IUA progression but delayed colonic injury, and Gal-3 combined with norepinephrine better promoted M2-like macrophage polarization and inhibited M1-like macrophage polarization. Together, these data indicated that MT-primed MSCs can ameliorate injury of both the uterus and colon in an IUA model through high Gal-3 expression to influence sympathetic nerves and in turn affect the polarization and recruitment of macrophages.
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