Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2024; 16(6): 708-727
Published online Jun 26, 2024. doi: 10.4252/wjsc.v16.i6.708
Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse
Lei-Mei Xu, Xin-Xin Yu, Ning Zhang, Yi-Song Chen
Lei-Mei Xu, Xin-Xin Yu, Ning Zhang, Yi-Song Chen, Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
Lei-Mei Xu, Department of Gynecology, Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai 200011, China
Author contributions: Xu LM designed the study, performed the experiments, analyzed the data and wrote the manuscript; Yu XX and Chen YS edited the manuscript; Zhang N performed the experiments involved in revision stage; Chen YS interpreted the data; and all the authors read and approved the manuscript.
Supported by the National Natural Science Foundation of China, No. 81671439; the Science and Technology Commission of Shanghai Municipality, No. 21Y11906700 and No. 20Y11907300; and the Medical Innovation Research Project of the Science and Technology Commission of Shanghai Municipality, No. 22Y11906500.
Institutional review board statement: After approval from the Obstetrics and Gynecology Hospital of Fudan University (No. 2023-106), full-thickness biopsy specimens (0.5 cm2) from the vaginal wall were obtained from patients who underwent laparoscopic-assisted vaginal hysterectomy. Informed consent was obtained from all participants.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets analyzed during the current study are available from the corresponding author upon reasonable request.
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: Yi-Song Chen, Doctor, Chief Doctor, Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, No. 128 Shenyang Road, Shanghai 200011, China. cys373900207@163.com
Received: January 23, 2024
Revised: March 23, 2024
Accepted: April 22, 2024
Published online: June 26, 2024
Processing time: 153 Days and 21.1 Hours
Abstract
BACKGROUND

Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.

AIM

To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved.

METHODS

Human vaginal wall collagen content was assessed by Masson’s trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules.

RESULTS

In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression.

CONCLUSION

HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.

Keywords: Pelvic organ prolapse; Exosomes; Fibroblasts; Human umbilical cord mesenchymal stromal cells; Extracellular matrix; Collagen I

Core Tip: Our original article, titled “Exosomes derived from hucMSCs promote the growth and collagen production of fibroblasts from pelvic organ prolapse through microRNAs” focused on a promising cell-free treatment for pelvic organ prolapse (POP). Our study the first demonstrated that human umbilical cord mesenchymal stromal cell-derived exosome (hucMSC-Exo) at certain concentrations could facilitate the growth and extracellular matrix remodeling of the primary fibroblasts from POP. Morever, microRNA sequencing of hucMSC-Exos and high-throughput RNA sequencing of fibroblasts exposed to hucMSC-Exos revealed that highly expressed exosomal microRNAs targeted and downregulated the expression of matrix metalloproteinase 11 in fibroblasts, leading to the increased production of collagen I. These results suggested that hucMSC-Exos could be a promising treatment for POP and may overcome current therapeutic difficulties.