Extracellular Vesicles Inhibit Proliferation and Invasion of Ovarian Endometrial Stromal Cells and Their Expression of SF-1, ERβ, and Aromatase

Xiaoqing Wang, Peili Wu, Xin Li, Cheng Zeng, Jingwen Zhu, Yingfang Zhou, Ye Lu, Qing Xue
Frontiers in endocrinology · 2021 · vol. 12 , pp. 666195 · doi:10.3389/fendo.2021.666195 · PMID:34531822 · W3196966364
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells inhibited proliferation and invasion of ovarian endometrial stromal cells and reduced their expression of SF-1, ERβ, and aromatase.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This study cultured human umbilical cord mesenchymal stem cells, isolated extracellular vesicles (EVs) by ultracentrifugation, and exposed ovarian endometrial stromal cells (ESCs) obtained from women with endometriosis to 120 μg/mL EVs, assessing proliferation, invasion, and expression of SF-1, ERβ, and aromatase along with cyclin D1 and MMP9. EV treatment significantly decreased cyclin D1 and MMP9 expression (mRNA and protein) and reduced ESC proliferation (CCK-8) and invasion (Transwell) compared with PBS controls. EVs also significantly lowered ESC levels of SF-1 (NR5A1), ERβ (ESR2), and aromatase (CYP19A1). A key limitation is that all findings are based on in vitro stimulation of patient-derived ESCs, with no in vivo or mechanistic EV cargo analysis reported. This paper is centrally about endometriosis — it tests UC-MSC-derived extracellular vesicles as inhibitors of endometriosis-relevant ESC proliferation, invasion, and estrogen-related gene/protein expression.

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Abstract

Objective: Endometriosis is an estrogen-dependent chronic disease. The abnormal proliferation and invasion of ectopic stromal cells (ESCs) are important manifestations of endometriosis, and it is necessary to find safer and more effective treatments. Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (UC-MSCs) have been shown to be promising for the treatment of many diseases, except endometriosis. The main purpose of this study was to explore the effect of EVs derived from UC-MSCs on ESCs and evaluate the therapeutic value of EVs on endometriosis. Study Design: Following the successful culture and identification of UC-MSCs, we collected the medium of UC-MSCs and extracted EVs by ultracentrifugation. Then, 120 μg/mL EVs were used to stimulate ESCs, which were collected to evaluate cell proliferation and invasion and expression of the estrogen-related proteins steroidogenic factor-1 (SF-1), estrogen receptors β (ERβ), and aromatase. Results: Compared with the control group treated with isodose phosphate buffered saline (PBS), 120 μg/mL EVs exposure significantly decreased the expression of cyclin D1 (mRNA: n = 6, P = 0.02; protein: n = 6, P = 0.000) and matrix metalloproteinase (MMP) 9 (mRNA: n = 6, P = 0.04; protein: n = 6, P = 0.000) of ESCs, which were consistent with Cell Counting Kit-8(CCK-8) results (day 0: NC: 0.29 ± 0.04, 120 μg/mL EVs: 0.28 ± 0.04; day 1: NC: 0.42 ± 0.08, 120 μg/mL EVs: 0.32 ± 0.01; day 2: NC: 0.64 ± 0.07, 120 μg/mL EVs: 0.50 ± 0.05, P = 0.000; day 3: NC: 0.82 ± 0.09, 120 μg/mL EVs: 0.65 ± 0.07, P = 0.000; day 4: NC: 0.95 ± 0.11, 120 μg/mL EVs: 0.76 ± 0.07, P = 0.012; n = 6) and Transwell experiments (n = 6, P = 0.000). In addition, the expression of SF-1 (encoded by NR5A1; mRNA: n = 6, P = 0.000; protein: n = 6, P = 0.000), ERβ (encoded by ESR2; mRNA: n = 6, P = 0.000; protein: n = 6, P = 0.000), and aromatase (encoded by CYP19A1; mRNA: n = 6, P = 0.04; protein: n = 6, P = 0.000) in ESCs decreased significantly. Conclusion: Taken together, the results show that 120 μg/mL EVs derived from UC-MSCs can effectively inhibit the proliferation and invasion of ESCs, as well as their expression of SF-1, ERβ and aromatase, and thus may lead to the alleviation of endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Cell Proliferation Endometriosis Endometrium Extracellular Vesicles Mesenchymal Stem Cells Ovary Stromal Cells Adult Aromatase Aromatase Case-Control Studies Cells, Cultured Endometriosis Endometriosis Endometriosis Endometrium Endometrium Estrogen Receptor beta Estrogen Receptor beta Extracellular Vesicles

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