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骨髓间充质干细胞来源外泌体中的miR-29a在宫腔粘连子宫内膜修复过程中抑制纤维化

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

作者信息

Tan Qingqing, Xia Dandan, Ying Xiaoyan

机构信息

Department of Gynecological Oncology, The Affiliated Changzhou Maternal and Child Health Care Hospital of Nanjing Medical University, Changzhou, China.

Department of Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

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

DOI:10.15283/ijsc20049
PMID:33250449
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7691861/
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 or . BMSCs-Exo overexpressing miR-29a can reduce SMA, 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.

摘要

背景与目的

骨髓间充质干细胞(BMSCs)是治疗宫腔粘连的理想干细胞来源。外泌体是一种膜泡,直径为30~100nm。外泌体可将其内容物带入靶细胞,释放并发挥其功能。在本研究中,我们旨在探讨人BMSC来源的外泌体(BMSC-Exo)在宫腔粘连治疗中促进子宫内膜损伤修复的作用。

方法

我们采用磁珠亲和法提取BMSC-Exo并分析其生物学特性。然后将BMSCs-Exo与子宫内膜细胞共培养以检测其效果。我们将BMSCs-Exo注射到宫腔粘连小鼠模型中。通过瞬时转染在BMSCs-Exo中过表达miR-29a,然后用RT-PCR分析相关基因的表达。

结果

BMSCs-Exo表达外泌体特异性蛋白CD9、CD63和CD81。BMSCs-Exo可将内容物带入靶细胞。BMSCs-Exo可促进子宫内膜修复。过表达miR-29a的BMSCs-Exo可降低平滑肌肌动蛋白(SMA)、Ⅰ型胶原、SMAD2和SMAD3。

结论

在本研究中,我们成功分离出BMSCs-Exo并证实了其特性和生物学活性。BMSCs-Exo在体外可促进细胞增殖和细胞迁移,并可修复宫腔粘连模型中受损的子宫内膜。BMSCs-Exo中miR-29a的存在可能是其在宫腔粘连子宫内膜修复过程中抗纤维化的重要因素。本研究为宫腔粘连患者的治疗提供了新思路,具有重要的临床研究意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/ddd1edcce3a8/IJSC-13-414-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/b1895b1a8c83/IJSC-13-414-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/46e3987d53ea/IJSC-13-414-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/cfb59c92f974/IJSC-13-414-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/ae957b787925/IJSC-13-414-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/ddd1edcce3a8/IJSC-13-414-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/b1895b1a8c83/IJSC-13-414-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/46e3987d53ea/IJSC-13-414-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/cfb59c92f974/IJSC-13-414-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/ae957b787925/IJSC-13-414-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/004f/7691861/ddd1edcce3a8/IJSC-13-414-f5.jpg

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