Secretion of WNT7A by UC-MSCs Assist in Promoting the Endometrial Epithelial Regeneration

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jul 1

PMID 38947517

Authors

Fangbo Liu

Qin Lin

Shaolei Shen

Zhihong Li

Xiaorui Xie

Quan Cheng

Lan Wang

Yin Long

Juan Wang

Li Liu

Affiliations

Soon will be listed here.

Abstract

Stem cell therapy for intrauterine adhesions (IUAs) has been widely used in clinical treatment. However, intravenous injection lacks sufficient targeting capabilities, while injection poses challenges in ensuring the effective survival of stem cells. Furthermore, the mechanism underlying the interaction between stem cells and endometrial cells remains poorly understood, and there is a lack of suitable models for studying these problems. Here, we designed an extracellular matrix (ECM)-adhesion mimic hydrogel for intrauterine administration, which was more effective than direct injection in treating IUAs. Additionally, we analyzed the epithelial-mesenchymal transition (EMT) and confirmed that the activation of endometrial epithelial stem cells is pivotal. Our findings demonstrated that umbilical cord mesenchymal stem cells (UC-MSCs) secrete WNT7A to activate endometrial epithelial stem cells, thereby accelerating regeneration of the endometrial epithelium. Concurrently, under transforming growth factor alpha (TGFA) stimulation secreted by the EMT epithelium, UC-MSCs upregulate E-cadherin while partially implanting into the endometrial epithelium.

References

Flum M, Dicks S, Teng Y, Schrempp M, Nystrom A, Boerries M . Canonical TGFβ signaling induces collective invasion in colorectal carcinogenesis through a Snail1- and Zeb1-independent partial EMT. Oncogene. 2022; 41(10):1492-1506. PMC: 8897192. DOI: 10.1038/s41388-022-02190-4. View

Xin L, Zheng X, Chen J, Hu S, Luo Y, Ge Q . An Acellular Scaffold Facilitates Endometrial Regeneration and Fertility Restoration via Recruiting Endogenous Mesenchymal Stem Cells. Adv Healthc Mater. 2022; 11(21):e2201680. DOI: 10.1002/adhm.202201680. View

Cen J, Zhang Y, Bai Y, Ma S, Zhang C, Jin L . Research progress of stem cell therapy for endometrial injury. Mater Today Bio. 2022; 16:100389. PMC: 9403503. DOI: 10.1016/j.mtbio.2022.100389. View

Masuda H, Anwar S, Buhring H, Rao J, Gargett C . A novel marker of human endometrial mesenchymal stem-like cells. Cell Transplant. 2012; 21(10):2201-14. DOI: 10.3727/096368911X637362. View

Su J, Ding L, Cheng J, Yang J, Li X, Yan G . Transplantation of adipose-derived stem cells combined with collagen scaffolds restores ovarian function in a rat model of premature ovarian insufficiency. Hum Reprod. 2016; 31(5):1075-86. DOI: 10.1093/humrep/dew041. View

Feng Y, Mrksich M . The synergy peptide PHSRN and the adhesion peptide RGD mediate cell adhesion through a common mechanism. Biochemistry. 2004; 43(50):15811-21. DOI: 10.1021/bi049174+. View

Lee W, Liu C, Cheng M, Chang W, Liu W, Wang P . Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision. Int J Mol Sci. 2021; 22(10). PMC: 8153321. DOI: 10.3390/ijms22105175. View

Tian X, Wang J, Jiang L, Jiang Y, Xu J, Feng X . Chemokine/GPCR Signaling-Mediated EMT in Cancer Metastasis. J Oncol. 2022; 2022:2208176. PMC: 9578795. DOI: 10.1155/2022/2208176. View

Shao X, Taha I, Clauser K, Gao Y, Naba A . MatrisomeDB: the ECM-protein knowledge database. Nucleic Acids Res. 2019; 48(D1):D1136-D1144. PMC: 6943062. DOI: 10.1093/nar/gkz849. View

10.

Schramm F, Schaefer L, Wygrecka M . EGFR Signaling in Lung Fibrosis. Cells. 2022; 11(6). PMC: 8947373. DOI: 10.3390/cells11060986. View

11.

Garcia J, Quiros M, Han W, OLeary M, Cox G, Nusrat A . IFN-γ-tethered hydrogels enhance mesenchymal stem cell-based immunomodulation and promote tissue repair. Biomaterials. 2019; 220:119403. PMC: 6717550. DOI: 10.1016/j.biomaterials.2019.119403. View

12.

Mucenski M, Mahoney R, Adam M, Potter A, Potter S . Single cell RNA-seq study of wild type and Hox9,10,11 mutant developing uterus. Sci Rep. 2019; 9(1):4557. PMC: 6418183. DOI: 10.1038/s41598-019-40923-w. View

13.

Huch M, Dorrell C, Boj S, van Es J, Li V, van de Wetering M . In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013; 494(7436):247-50. PMC: 3634804. DOI: 10.1038/nature11826. View

14.

Tempest N, Maclean A, Hapangama D . Endometrial Stem Cell Markers: Current Concepts and Unresolved Questions. Int J Mol Sci. 2018; 19(10). PMC: 6214006. DOI: 10.3390/ijms19103240. View

15.

Jiang Y, Zhang H, Wang J, Liu Y, Luo T, Hua H . Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy. J Hematol Oncol. 2022; 15(1):34. PMC: 8943941. DOI: 10.1186/s13045-022-01252-0. View

16.

Cindrova-Davies T, Zhao X, Elder K, Jones C, Moffett A, Burton G . Menstrual flow as a non-invasive source of endometrial organoids. Commun Biol. 2021; 4(1):651. PMC: 8211845. DOI: 10.1038/s42003-021-02194-y. View

17.

Xiao M, Qiu J, Kuang R, Zhang B, Wang W, Yu Q . Synergistic effects of stromal cell-derived factor-1α and bone morphogenetic protein-2 treatment on odontogenic differentiation of human stem cells from apical papilla cultured in the VitroGel 3D system. Cell Tissue Res. 2019; 378(2):207-220. DOI: 10.1007/s00441-019-03045-3. View

18.

Fonseca M, Haro M, Wright K, Lin X, Abbasi F, Sun J . Single-cell transcriptomic analysis of endometriosis. Nat Genet. 2023; 55(2):255-267. PMC: 10950360. DOI: 10.1038/s41588-022-01254-1. View

19.

Esfandyari S, Chugh R, Park H, Hobeika E, Ulin M, Al-Hendy A . Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility. Cells. 2020; 9(10). PMC: 7599919. DOI: 10.3390/cells9102253. View

20.

Im S, Kim C, Jung Y, Jang Y, Kim S . Biodegradable vascular stents with high tensile and compressive strength: a novel strategy for applying monofilaments via solid-state drawing and shaped-annealing processes. Biomater Sci. 2017; 5(3):422-431. DOI: 10.1039/c7bm00011a. View