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揭示多能干细胞样细胞向卵巢膜细胞分化的潜能。

Unveiling the Differentiation Potential of Ovarian Theca Interna Cells from Multipotent Stem Cell-like Cells.

机构信息

Pôle de Recherche en Physiopathologie de la Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Hippocrate 54, bte B1.55.03, 1200 Brussels, Belgium.

出版信息

Cells. 2024 Jul 25;13(15):1248. doi: 10.3390/cells13151248.

Abstract

RESEARCH QUESTION

Theca interna cells (TICs) are an indispensable cell source for ovarian follicle development and steroidogenesis. Recent studies have identified theca stem cells (TSCs) in both humans and animals. Interestingly, TSCs express mesenchymal stem cell (MSC)-related markers and can differentiate into mesenchymal lineages. MSCs are promising for tissue engineering and regenerative medicine due to their self-renewal and differentiation abilities. Therefore, this study investigated the potential origin of TICs from MSCs.

DESIGN

Whole ovaries from postmenopausal organ donors were obtained, and their cortex was cryopreserved prior to the isolation of stromal cells. These isolated cells were differentiated in vitro to TICs using cell media enriched with various growth factors and hormones. Immunocytochemistry, an enzyme-linked immunosorbent assay, flow cytometry, and reverse transcription-quantitative polymerase chain were employed at different timepoints. Data were analyzed using one-way ANOVA.

RESULTS

Immunocytochemistry showed an increase in TIC markers from day 0 to day 8 and a significant rise in MSC-like markers on day 2. This corresponds with rising androstenedione levels from day 2 to day 13. Flow cytometry identified a decreasing MSC-like cell population from day 2 onwards. The CD13+ cell population and its gene expression increased significantly over time. NGFR and PDGFRA expression was induced on days 0 and 2, respectively, compared to day 13.

CONCLUSIONS

This study offers insights into MSC-like cells as the potential origin of TICs. Differentiating TICs from these widely accessible MSCs holds potential significance for toxicity studies and investigating TIC-related disorders like polycystic ovary syndrome (PCOS).

摘要

研究问题

内膜细胞(TICs)是卵泡发育和类固醇生成所必需的细胞来源。最近的研究在人和动物中都发现了膜细胞干细胞(TSCs)。有趣的是,TSCs 表达间充质干细胞(MSC)相关标记物,并能分化为间充质谱系。由于具有自我更新和分化能力,MSC 有望用于组织工程和再生医学。因此,本研究探讨了 TICs 起源于 MSC 的可能性。

设计

从绝经后器官捐献者获得整个卵巢,并在分离基质细胞之前对其皮质进行冷冻保存。这些分离的细胞在体外使用富含各种生长因子和激素的细胞培养基分化为 TICs。在不同时间点采用免疫细胞化学、酶联免疫吸附试验、流式细胞术和反转录-定量聚合酶链式反应进行检测。采用单因素方差分析进行数据分析。

结果

免疫细胞化学显示 TIC 标志物从第 0 天到第 8 天增加,第 2 天 MSC 样标志物显著增加。这与第 2 天到第 13 天雄烯二酮水平的升高相对应。流式细胞术显示第 2 天以后 MSC 样细胞群体逐渐减少。CD13+细胞群体及其基因表达随时间显著增加。NGFR 和 PDGFRA 的表达分别在第 0 天和第 2 天诱导,而在第 13 天则没有。

结论

本研究为 MSC 样细胞作为 TICs 的潜在起源提供了新的见解。从这些广泛可获得的 MSC 中分化 TICs,对于毒性研究和研究与 TIC 相关的疾病(如多囊卵巢综合征(PCOS))具有潜在的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/769a/11311681/169c3b3bb23a/cells-13-01248-g001.jpg

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