miR-29a in Exosomes from Bone Marrow Mesenchymal Stem Cells Inhibit Fibrosis during Endometrial Repair of Intrauterine Adhesion

Int J Stem Cells. 2020 Nov 30;13(3):414-423. doi: 10.15283/ijsc20049.

Abstract

Background and objectives: Bone marrow mesenchymal stem cells (BMSCs) is an ideal source of stem cells in the treatment of intrauterine adhesion. Exosomes are a type of membrane vesicle and the diameter is 30∼100 nm. Exosomes can take their contents into the target cells, releasing and exerting their functions. In this study, we intend to study the role of human BMSC-derived exosomes (BMSC-Exo) in promoting endometrial damage repair in the treatment of IUA.

Methods: We used the magnetic bead affinity method to extract BMSC-Exo and analyzed its biological character. Then we co-cultured the BMSCs-Exo with endometrial cells to detect its effect. We injected BMSCs-Exo into the IUA mouse model. We over-expressed miR-29a in BMSCs-Exo by transient transfection, then used RT-PCR to analyze the expression of the related genes.

Results: BMSCs-Exo expressed exosome-specific proteins CD9, CD63, and CD81. BMSCs-Exo could bring the contents into the target cells. BMSCs-Exo can promote endometrial repair in vitro or in vivo. BMSCs-Exo overexpressing miR-29a can reduce αSMA, Collagen I, SMAD2, and SMAD3.

Conclusions: In this study, we successfully isolated BMSCs-Exo and proved its character and biological activity. BMSCs-Exo can promote cell proliferation and cell migration in vitro and can repair damaged endometrium in the IUA model. The presence of miR-29a in BMSCs-Exo may be an important factor in its resistance to fibrosis during endometrial repair of IUA. This study provides new ideas for the treatment of patients with IUA and has important clinical research significance.

Keywords: Anti-fibrosis; Bone marrow mesenchymal stem cells; Exosomes; miR-29α.