hUMSCs Restore Uterine Function by Inhibiting Endometrial Fibrosis via Regulation of the MMP-9/TIMP-1 Ratio in CDDP-Induced Injury Rats

Yu Tang; Yaru Si; Chengen Liu; Cui Li; Li Qu; Ying Liu; Qiang Fu; Qianqian Luo

doi:10.1155/2023/8014052

hUMSCs Restore Uterine Function by Inhibiting Endometrial Fibrosis via Regulation of the MMP-9/TIMP-1 Ratio in CDDP-Induced Injury Rats

Stem Cells Int. 2023 Mar 20:2023:8014052. doi: 10.1155/2023/8014052. eCollection 2023.

Authors

Yu Tang¹, Yaru Si², Chengen Liu³, Cui Li⁴, Li Qu⁴, Ying Liu⁴, Qiang Fu^{2

5}, Qianqian Luo¹

Affiliations

¹ College of Basic Medicine, Binzhou Medical University, Yantai, Shandong 264003, China.
² School of Pharmacology, Institute of Aging Medicine, Binzhou Medical University, Yantai, Shandong 264003, China.
³ Clinical Medical School, Binzhou Medical University, Yantai, Shandong 264003, China.
⁴ Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, China.
⁵ Shandong Cellogene Medicine Science & Technology Co., Ltd., Yantai, Shandong 264003, China.

Abstract

The fertility of females of childbearing age who are cured of cancer by chemotherapy is gradually declining globally. As a broad-spectrum chemotherapy drug in clinic, the damage of cisplatin (CDDP) to female reproductive function cannot be ignored. At present, the study of CDDP damage to the uterus is not sufficient, and the exact mechanism needs to be further explored. Therefore, we conducted this research to determine whether uterine injury in CDDP-induced injury rats might be improved by human umbilical cord mesenchymal stem cells (hUMSCs) and to further explore the precise mechanism. The rat model of CDDP-induced injury was established by intraperitoneal injection of CDDP, and hUMSCs were injected into the tail vein 7 days later. In vivo, uterine function in CDDP-induced injury rats was affected after hUMSC transplantation. In vitro, the specific mechanism was further explored from the cell and protein levels. Overall, the specific reason of CDDP-induced uterine dysfunction in rats was endometrial fibrosis, which was significantly improved after hUMSC transplantation. Further investigation of the mechanism found that hUMSCs could regulate the ratio of matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in endometrial stromal cells (EnSCs) after CDDP injury.