Human umbilical cord mesenchymal stem cells derived extracellular vesicles alleviate salpingitis by promoting M1-to-M2 transformation

Changlin Zhang; Wei Liao; Weizhao Li; Mengxiong Li; Xiaoyu Xu; Haohui Sun; Yaohua Xue; Lixiang Liu; Jiehong Qiu; Chi Zhang; Xunzhi Zhang; Juntong Ye; Jingran Du; David Y B Deng; Wuguo Deng; Tian Li

doi:10.3389/fphys.2023.1131701

Human umbilical cord mesenchymal stem cells derived extracellular vesicles alleviate salpingitis by promoting M1-to-M2 transformation

Front Physiol. 2023 Feb 16:14:1131701. doi: 10.3389/fphys.2023.1131701. eCollection 2023.

Authors

Changlin Zhang¹, Wei Liao¹, Weizhao Li¹, Mengxiong Li¹, Xiaoyu Xu¹, Haohui Sun², Yaohua Xue³, Lixiang Liu¹, Jiehong Qiu¹, Chi Zhang¹, Xunzhi Zhang⁴, Juntong Ye¹, Jingran Du¹, David Y B Deng¹, Wuguo Deng², Tian Li¹

Affiliations

¹ Pelvic Floor Disorders Center, Scientific Research Center, Department of Gynecology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
² Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
³ Department of Clinical Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China.
⁴ College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.

Abstract

Background: With an increasing number of patients experiencing infertility due to chronic salpingitis after Chlamydia trachomatis (CT) infection, there is an unmet need for tissue repair or regeneration therapies. Treatment with human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EV) provides an attractive cell-free therapeutic approach. Methods: In this study, we investigated the alleviating effect of hucMSC-EV on tubal inflammatory infertility caused by CT using in vivo animal experiments. Furthermore, we examined the effect of hucMSC-EV on inducing macrophage polarization to explore the molecular mechanism. Results: Our results showed that tubal inflammatory infertility caused by Chlamydia infection was significantly alleviated in the hucMSC-EV treatment group compared with the control group. Further mechanistic experiments showed that the application of hucMSC-EV induced macrophage polarization from the M1 to the M2 type via the NF-κB signaling pathway, improved the local inflammatory microenvironment of fallopian tubes and inhibited tube inflammation. Conclusion: We conclude that this approach represents a promising cell-free avenue to ameliorate infertility due to chronic salpingitis.

Keywords: NF-κB signaling pathway; chronic salpingitis; extracellular vesicles; macrophage polarization; mesenchymal stem cell (MSC).

Grants and funding

This work was supported by funds from the National Natural Science Foundation of China (82002899, 82172883, 82001498), the Guangdong Basic and Applied Basic Research Foundation (2019A1515110085, 2022A1515012444), and the Open Funds of State Key Laboratory of Oncology in South China (HN 2021-05).