Lin F, Ding Y, Ma KX, Liang XT. Clarifying the role of exosomal miR-137-3p in endometrial regeneration: Mechanistic gaps and future directions. World J Stem Cells 2025; 17(6): 109283 [DOI: 10.4252/wjsc.v17.i6.109283]
Corresponding Author of This Article
Xiao-Ting Liang, MD, PhD, Associate Researcher, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China. liangxt@tongji.edu.cn
Research Domain of This Article
Cell Biology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Jun 26, 2025; 17(6): 109283 Published online Jun 26, 2025. doi: 10.4252/wjsc.v17.i6.109283
Clarifying the role of exosomal miR-137-3p in endometrial regeneration: Mechanistic gaps and future directions
Fang Lin, Yue Ding, Ke-Xin Ma, Xiao-Ting Liang
Fang Lin, Ke-Xin Ma, Xiao-Ting Liang, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Yue Ding, Department of Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200000, China
Ke-Xin Ma, Shanghai East Hospital, Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China
Xiao-Ting Liang, Shenzhen Ruipuxun Academy for Stem Cell and Regenerative Medicine, Shenzhen 518025, Guangdong Province, China
Co-first authors: Fang Lin and Yue Ding.
Author contributions: Lin F and Ding Y contributed equally to this work as co-first authors. Lin F and Ding Y drafted the manuscript and conducted the literature analysis; Ma KX participated in revision of the content and contributed to institutional coordination; Liang XT conceived the concept, supervised the project, and provided final approval of the version to be submitted. All authors reviewed and approved the final manuscript.
Supported by the General Program of the Natural Science Foundation of Guangdong Province, No. 2025A1515011163.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Ting Liang, MD, PhD, Associate Researcher, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China. liangxt@tongji.edu.cn
Received: May 7, 2025 Revised: May 21, 2025 Accepted: June 12, 2025 Published online: June 26, 2025 Processing time: 50 Days and 1.7 Hours
Abstract
This article comments on the study by Zhang et al, which proposed that exosomes derived from hypoxia-injured endometrial epithelial cells promote human umbilical cord mesenchymal stem cell migration and differentiation into endometrial epithelial cells via exosomal miR-137-3p. The authors demonstrated that miR-137-3p targets ubiquitin protein ligase E3C and activates signal transducer and activator of transcription 3 signaling, thereby driving epithelial lineage transition. While this study expands our understanding of exosome-mediated intercellular communication in endometrial repair, several key gaps remain. Notably, microRNA (miRNA) profiling was performed in human umbilical cord mesenchymal stem cells post-exosome treatment, not in the exosomes derived from hypoxia-injured endometrial epithelial cell themselves, leaving open whether miR-137-3p is directly transferred or indirectly induced. In addition, data on exosome characterization were unavailable, and the rationale for selecting miR-137-3p over other differentially expressed miRNAs was not well justified. Future studies should include direct exosomal miRNA content analysis, in vivo validation, and deeper mechanistic exploration of the ubiquitin protein ligase E3C-signal transducer and activator of transcription 3 ubiquitination axis to establish the clinical and biological relevance of this pathway.
Core Tip: This commentary examines the study by Zhang et al on exosomal miR-137-3p-mediated endometrial regeneration. While the proposed mechanism involving ubiquitin protein ligase E3C inhibition and signal transducer and activator of transcription 3 activation is compelling, several issues remain unresolved, including the unclear source of miR-137-3p, lack of exosome characterization, and absence of in vivo validation. We highlight the need for direct evidence of exosomal microRNA transfer, mechanistic exploration of the ubiquitin protein ligase E3C-signal transducer and activator of transcription 3 ubiquitination axis, and functional evaluation in animal models to substantiate the therapeutic relevance of this approach.
