Human Umbilical Cord Mesenchymal Stem Cells Derived Extracellular Vesicles Alleviate Salpingitis by Promoting M1-to-M2 Transformation

Overview

Journal Front Physiol

Date 2023 Mar 6

PMID 36875046

Authors

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

Affiliations

Soon will be listed here.

Abstract

With an increasing number of patients experiencing infertility due to chronic salpingitis after (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. In this study, we investigated the alleviating effect of hucMSC-EV on tubal inflammatory infertility caused by CT using animal experiments. Furthermore, we examined the effect of hucMSC-EV on inducing macrophage polarization to explore the molecular mechanism. Our results showed that tubal inflammatory infertility caused by 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 the NF-κB signaling pathway, improved the local inflammatory microenvironment of fallopian tubes and inhibited tube inflammation. We conclude that this approach represents a promising cell-free avenue to ameliorate infertility due to chronic salpingitis.

Citing Articles

Application of adult stem cells in obstetrics and gynecology: A scoping review.

Kurniadi A, Zucha M, Kusumanto A, Salima S, Harsono A Eur J Obstet Gynecol Reprod Biol X. 2025; 25:100367.

PMID: 39967607 PMC: 11833614. DOI: 10.1016/j.eurox.2025.100367.

Human umbilical cord mesenchymal stem cells small extracellular vesicles-derived miR-370-3p inhibits cervical precancerous lesions by targeting DHCR24.

Li W, Zhang C, Gao T, Sun Y, Yang H, Liu L Stem Cells Transl Med. 2024; 14(1).

PMID: 39552565 PMC: 11825698. DOI: 10.1093/stcltm/szae087.

Engineered extracellular vesicles for tissue repair and regeneration.

Zhang Y, Wu D, Zhou C, Bai M, Wan Y, Zheng Q Burns Trauma. 2024; 12:tkae062.

PMID: 39439545 PMC: 11495891. DOI: 10.1093/burnst/tkae062.

Emerging Role and Mechanism of Mesenchymal Stem Cells-Derived Extracellular Vesicles in Rheumatic Disease.

Wang Z, Yang C, Yan S, Sun J, Zhang J, Qu Z J Inflamm Res. 2024; 17:6827-6846.

PMID: 39372581 PMC: 11451471. DOI: 10.2147/JIR.S488201.

Effect of lyophilized exosomes derived from umbilical cord stem cells on chronic anterior cruciate ligament cell injury.

Lo H, Lin S, Ho C, Ming-Kung Y, Lu C J Orthop Surg Res. 2024; 19(1):554.

PMID: 39252098 PMC: 11382386. DOI: 10.1186/s13018-024-05029-8.

References

Cai G, Cai G, Zhou H, Zhuang Z, Liu K, Pei S . Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction. Stem Cell Res Ther. 2021; 12(1):2. PMC: 7786953. DOI: 10.1186/s13287-020-02030-w. View

Xin L, Lin X, Zhou F, Li C, Wang X, Yu H . A scaffold laden with mesenchymal stem cell-derived exosomes for promoting endometrium regeneration and fertility restoration through macrophage immunomodulation. Acta Biomater. 2020; 113:252-266. DOI: 10.1016/j.actbio.2020.06.029. View

Lai G, Zhao R, Zhuang W, Hou Z, Yang Z, He P . BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats. PeerJ. 2022; 10:e13744. PMC: 9509671. DOI: 10.7717/peerj.13744. View

Joo H, Suh J, Lee H, Bang E, Lee J . Current Knowledge and Future Perspectives on Mesenchymal Stem Cell-Derived Exosomes as a New Therapeutic Agent. Int J Mol Sci. 2020; 21(3). PMC: 7036914. DOI: 10.3390/ijms21030727. View

Ullah M, Liu D, Rai S, Razavi M, Concepcion W, Thakor A . Pulsed focused ultrasound enhances the therapeutic effect of mesenchymal stromal cell-derived extracellular vesicles in acute kidney injury. Stem Cell Res Ther. 2020; 11(1):398. PMC: 7490886. DOI: 10.1186/s13287-020-01922-1. View

Cui G, Wu J, Mou F, Xie W, Wang F, Wang Q . Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. FASEB J. 2017; 32(2):654-668. DOI: 10.1096/fj.201700600R. View

Li L, Yu R, Cai T, Chen Z, Lan M, Zou T . Effects of immune cells and cytokines on inflammation and immunosuppression in the tumor microenvironment. Int Immunopharmacol. 2020; 88:106939. DOI: 10.1016/j.intimp.2020.106939. View

Hayden M, Ghosh S . NF-κB in immunobiology. Cell Res. 2011; 21(2):223-44. PMC: 3193440. DOI: 10.1038/cr.2011.13. View

Qian M, Wang S, Guo X, Wang J, Zhang Z, Qiu W . Hypoxic glioma-derived exosomes deliver microRNA-1246 to induce M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-κB pathways. Oncogene. 2019; 39(2):428-442. DOI: 10.1038/s41388-019-0996-y. View

10.

Teng L, Maqsood M, Zhu M, Zhou Y, Kang M, Zhou J . Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Diabetic Wound Healing via Promoting M2 Macrophage Polarization, Angiogenesis, and Collagen Deposition. Int J Mol Sci. 2022; 23(18). PMC: 9498995. DOI: 10.3390/ijms231810421. View

11.

Gao Y, Xu Z, Li X, Liu Z, Li W, Kang Y . Resibufogenin, one of bufadienolides in toad venom, suppresses LPS-induced inflammation via inhibiting NF-κB and AP-1 pathways. Int Immunopharmacol. 2022; 113(Pt A):109312. DOI: 10.1016/j.intimp.2022.109312. View

12.

Reis M, Willis G, Fernandez-Gonzalez A, Yeung V, Taglauer E, Magaletta M . Mesenchymal Stromal Cell-Derived Extracellular Vesicles Restore Thymic Architecture and T Cell Function Disrupted by Neonatal Hyperoxia. Front Immunol. 2021; 12:640595. PMC: 8082426. DOI: 10.3389/fimmu.2021.640595. View

13.

Pluchino S, Smith J . Explicating Exosomes: Reclassifying the Rising Stars of Intercellular Communication. Cell. 2019; 177(2):225-227. DOI: 10.1016/j.cell.2019.03.020. View

14.

Meng F, Xu R, Wang S, Xu Z, Zhang C, Li Y . Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial. Signal Transduct Target Ther. 2020; 5(1):172. PMC: 7450163. DOI: 10.1038/s41392-020-00286-5. View

15.

Zhang M, Liu Z, Aoshima K, Cai W, Sun H, Xu T . CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression. Sci Transl Med. 2022; 14(630):eabf5473. PMC: 9003667. DOI: 10.1126/scitranslmed.abf5473. View

16.

Lin Z, Wu Y, Xu Y, Li G, Li Z, Liu T . Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential. Mol Cancer. 2022; 21(1):179. PMC: 9468526. DOI: 10.1186/s12943-022-01650-5. View

17.

Cooke J . Inflammation and Its Role in Regeneration and Repair. Circ Res. 2019; 124(8):1166-1168. PMC: 6578588. DOI: 10.1161/CIRCRESAHA.118.314669. View

18.

Harrell C, Jovicic N, Djonov V, Arsenijevic N, Volarevic V . Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases. Cells. 2019; 8(12). PMC: 6952783. DOI: 10.3390/cells8121605. View

19.

Markov A, Thangavelu L, Aravindhan S, Zekiy A, Jarahian M, Chartrand M . Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders. Stem Cell Res Ther. 2021; 12(1):192. PMC: 7971361. DOI: 10.1186/s13287-021-02265-1. View

20.

Ling H, Luo L, Dai X, Chen H . Fallopian tubal infertility: the result of Chlamydia trachomatis-induced fallopian tubal fibrosis. Mol Cell Biochem. 2021; 477(1):205-212. DOI: 10.1007/s11010-021-04270-7. View