ATI-2341 Trifluoroacetic Acid (TFA) Promotes Menstrual Blood-Derived Mesenchymal Stem Cell Recruitment and Enhances Uterine Repair Through Gi Pathway in Asherman’s Syndrome

Abstract

This study aimed to explore the role of ATI-2341 in Asherman’s syndrome and its impact on menstrual blood-derived mesenchymal stem cells (MenSCs). Following establishment of endometrial injury model, MenSCs were extracted from rats and cultured. They were treated with ATI-2341 TFA at different concentrations (10 ng/mL, 50 ng/mL, 100 ng/mL) and MenSCs treated without ATI-2341 TFA were taken as controls. Flow cytometry was conducted to detect the cell cycle. MTT was carried out to evaluate proliferation of endometrial cells. The expression levels of MMP-9, TIMP-1, CK, and VIM were determined with staining used to reflect morphology of endometrium. Administration with ATI-2341 TFA resulted in decreased expression of MMP-9 and increased expression of TIMP-1 in a dose-dependent manner. Of note, the increase of ATI-2341 TFA concentration was accompanied with elevated cell proliferation rate, increased number of glands in the endometrium, and decreased fibrosis area. As treated with 100 ng/mL ATI-2341 TFA, the cells exhibited more glands than that under other concentrations with uniformly arranged glands and lowest expression levels of CK and VIM, control group had plenty of blue-stained collagen fibers in the intima and least amount of glands. ATI-2341 TFA 100 ng/mL induced endometrial epithelial recruitment effect on MenSCs and promoted endometrial repair more significantly than Gi-3 pathway agonists. Collectively, ATI-2341 TFA enhances MenSC recruitment and facilitates endometrial epithelial cells proliferation and the repair of uterine damage in Asherman’s syndrome through Gi pathway. These findings provide a\ novel insight into the MenSC-based treatment against Asherman’s syndrome and deserve further investigation.