ATI-2341 TFA promotes repair of damaged endometrium by mediating the differentiation of bone marrow mesenchymal stem cells

Abstract

Intrauterine adhesion (IUA) is a common complication in endometrial disorder. This study investigated the role of ATI-2341, a functionally selective allosteric regulator of CXCR4 in IUAs, and its interaction with bone marrow-derived mesenchymal stem cells (BMSCs). Following establishment of endometrial injury model, rats BMSCs were treated with ATI-2341 TFA (100 ng/mL). Endometrial tissues of rats with IUA were treated with BMSCs and estrogen, or untreated which was taken as controls. The endometrium thickness was examined and endometrial BMSC proliferation was detected by MTT assay. Levels of MMP-9, TIMP-1, CK, and VIM were determined by Western blot analysis. Treatment with ATI-2341 TFA resulted in significantly decreased level of MMP-9 (0.346±0.036 ng/mL), compared with estrogen treatment (0.467±0.029 ng/mL) and control treatment. Both BMSCs carrying ATI-2341 TFA and estrogen induced increased expression of TIMP-1 (0.734±0.034 ng/mL, 0.618±0.035 ng/mL) and enhanced endometrim growth with thicker endometrium in ATI-2341 TFA group (294.21±59.97 μm). 48 h and 72 h after treatment, ATI-2341 TFA group and estrogen group exhibited increased proliferation rate (P <0.05), and higher rate appeared upon ATI-2341 TFA treatment. Cells in ATI-2341 TFA100 ng/mL and estrogen group were greatly positive for keratin and negative for vimentin. Collectively, ATI-2341 TFA promotes the differentiation of BMSCs into endometrial epithelial cells, enhances repair of damaged endometrium, and alleviate IUA. These findings might underlie a foundation for BMSC-based treatment for endometrial disorder.