Different Effect of Dienogest on Endometrium Mesenchymal Stem Cells Derived from Healthy and Endometriosis Tissues

IF 1.9 4区医学 Q2 MEDICINE, GENERAL & INTERNAL Balkan Medical Journal Pub Date : 2024-10-31 Epub Date: 2024-09-18 DOI:10.4274/balkanmedj.galenos.2024.2024-6-95

Hayal Uzelli Şimşek, Turgay Şimşek, Gökhan Duruksu, Selenay Furat Rençber, Yusufhan Yazır

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Abstract

Background: Endometriosis (EM) is an inflammatory condition in which the endometrium is observed to develop outside the uterine cavity. Endometrium has conventionally been recognized as a rich source of endometrial mesenchymal stem cells (E-MSCs). The influence of dienogest, a medication frequently prescribed for EM, on E-MSCs has not been extensively investigated.

Aims: To explore effects of dienogest on the E-MSCs derived from healthy (E-MSCs-control) and diseased (E-MSCs-endometriosis) endometrial tissue samples in vitro.

Study design: In vitro study.

Methods: We collected samples from healthy and diseased endometrial tissues. E-MSCs were derived from both healthy and EM tissues. The effect of dienogest (VISANNE) on E-MSCs was assessed by examining cell proliferation, telomerase activity, cell migration, and estrogen secretion levels after the isolation and characterization of E-MSCs.

Results: We discovered that cellular proliferation rate was higher in the E-MSCs derived from EM tissues compared to those derived from healthy tissue. The proliferation rate and telomerase activity were both suppressed by dienogest treatment, particularly in E-MSCs-endometriosis. The drug treatment also resulted in a decrease in the migration capacity of E-MSCs-endometriosis, from 60.4% to 59.2%. The expression of CXCL12, Ki67, and beta-catenin was analyzed in both E-MSCs-endometriosis and E-MSCs-control. The CXCL12 and Ki67 expressions were quite elevated in the E-MSCs-endometriosis without drug treatment compared to the E-MSCs-control. Following the treatment, these levels declined drastically to the levels close to E-MSCs-control. Similarly, this decrease in gene expression was accompanied by a decrease in estrogen secretion into the medium.

Conclusion: This research demonstrates that dienogest exerts a substantial impact on both stromal and stem cells, as it effectively controls the disease by reversing EM markers, despite the absence of progesterone receptors on endometrial stem cells.

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地诺孕对从健康组织和子宫内膜异位症组织中提取的子宫内膜间充质干细胞的不同影响

背景：子宫内膜异位症（EM）是一种子宫内膜在子宫腔外发育的炎症。子宫内膜一直被认为是子宫内膜间充质干细胞（E-MSCs）的丰富来源。由于间充质干细胞能分泌蛋白质和其他调节组织功能的因子，因此对再生医学中的组织平衡和修复至关重要。目的：探讨地诺孕酮对从健康（地诺孕酮-对照组）和患病（地诺孕酮-子宫内膜异位症）子宫内膜组织样本中提取的地诺孕酮间充质干细胞的影响。主要结果是，基于二烯孕酮的治疗方法也可设计为针对子宫内膜组织中的干细胞，从而使其能够有效调节疾病进展：研究设计：体外研究：我们收集了健康和患病子宫内膜组织的样本。E-MSCs来源于健康和EM组织。在分离和鉴定 E-MSCs 后，通过检测细胞增殖、端粒酶活性、细胞迁移和雌激素分泌水平，评估地诺孕酮（VISANNE）对 E-MSCs 的影响：结果：我们发现，与来自健康组织的干细胞相比，来自EM组织的干细胞的细胞增殖率更高。增殖率和端粒酶活性均受到双烯孕酮治疗的抑制，尤其是在子宫内膜异位症 E-MSCs 中。药物治疗还导致 E-MSCs-endometriosis 的迁移能力下降，从 60.4% 降至 59.2%。研究人员分析了子宫内膜异位症间充质干细胞和对照组间充质干细胞中CXCL12、Ki67和β-catenin的表达情况。与 E-MSCs 对照组相比，未经药物治疗的 E-MSCs-endometriosis 中 CXCL12 和 Ki67 的表达明显升高。治疗后，这些表达水平急剧下降至接近 E-MSCs 对照组的水平。同样，基因表达的减少也伴随着分泌到培养基中的雌激素的减少：这项研究表明，地诺孕酮对基质细胞和干细胞都有重大影响，因为尽管子宫内膜干细胞上没有孕激素受体，但地诺孕酮能通过逆转EM标志物有效控制疾病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Balkan Medical Journal MEDICINE, GENERAL & INTERNAL-

CiteScore

4.10

自引率

6.70%

发文量

审稿时长

6-12 weeks

期刊介绍： The Balkan Medical Journal (Balkan Med J) is a peer-reviewed open-access international journal that publishes interesting clinical and experimental research conducted in all fields of medicine, interesting case reports and clinical images, invited reviews, editorials, letters, comments and letters to the Editor including reports on publication and research ethics. The journal is the official scientific publication of the Trakya University Faculty of Medicine, Edirne, Turkey and is printed six times a year, in January, March, May, July, September and November. The language of the journal is English. The journal is based on independent and unbiased double-blinded peer-reviewed principles. Only unpublished papers that are not under review for publication elsewhere can be submitted. Balkan Medical Journal does not accept multiple submission and duplicate submission even though the previous one was published in a different language. The authors are responsible for the scientific content of the material to be published. The Balkan Medical Journal reserves the right to request any research materials on which the paper is based. The Balkan Medical Journal encourages and enables academicians, researchers, specialists and primary care physicians of Balkan countries to publish their valuable research in all branches of medicine. The primary aim of the journal is to publish original articles with high scientific and ethical quality and serve as a good example of medical publications in the Balkans as well as in the World.