Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse

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.

Key Words: 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.

• Citation: Xu LM, Yu XX, Zhang N, Chen YS. Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse. World J Stem Cells 2024; 16(6): 708-727
• URL: https://www.wjgnet.com/1948-0210/full/v16/i6/708.htm
• DOI: https://dx.doi.org/10.4252/wjsc.v16.i6.708