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评估来源于不孕妇女的人月经血源性干细胞向卵母细胞样细胞的分化潜能。

Evaluating differentiation potential of the human menstrual blood-derived stem cells from infertile women into oocyte-like cells.

机构信息

Department of Mesenchymal Stem Cells, Academic Center for Education, Culture and Research, Qom Branch, Qom, Iran.

Department of Reproductive Biology, Academic Center for Education, Culture and Research, Qom Branch, Qom, Iran.

出版信息

Reprod Biol. 2021 Mar;21(1):100477. doi: 10.1016/j.repbio.2020.100477. Epub 2021 Jan 2.

Abstract

One of the most intricate infertility problems among women is the number and quality of the oocytes. Menstrual blood-derived stem cells (MenSCs) are a recently discovered source of mesenchymal stem cells which is known as a suitable source of cells for regenerative medicine. We aimed to investigate whether MenSCs as autologous cell source from endometriosis, PCOS, and healthy women have different characteristics regarding their morphology, CD marker expression pattern, differentiation potential into oocyte-like cells, and oocyte-related genes expression. Menstrual blood samples (1-2 ml) from healthy and infertile women (PCOS and endometriosis) in the age range of 22-35 years were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation method was characterized by flow cytometry. MenSCs were induced under 20 % follicular fluid (FF), and then they were evaluated for differentiation by Real time-PCR and immunocytochemistry assay. MenSCs derived from endometriosis women had different morphology from PCOS and healthy women, but similar regarding their CD marker pattern. All induced MenSCs showed morphological changes and expressed oocyte related genes (STELLA, GDF9, STRA8, PRDM, LHR, FSHR, SCP3, DDX4, and ZP2) in the 2nd week of culture, but there was a significant difference between the groups. Endometriosis-derived MenSCs showed higher levels of both gene and protein expressions. These findings propose that MenSCs derived from endometriosis and PCOS patients under 20 % FF, not only could differentiate into oocyte-like cells, but also showed more differential potential in comparison with healthy women. This indicates the possibility of using the patients' own MenSCs to differentiate into the oocyte-like cells.

摘要

女性不孕问题中最复杂的问题之一是卵母细胞的数量和质量。月经血源性干细胞(MenSCs)是一种最近发现的间充质干细胞来源,被认为是再生医学的合适细胞来源。我们旨在研究来源于子宫内膜异位症、PCOS 和健康女性的 MenSCs 作为自体细胞来源,在形态、CD 标志物表达模式、向卵母细胞样细胞分化的潜能以及卵母细胞相关基因表达方面是否具有不同的特征。采集年龄在 22-35 岁之间的健康和不孕女性(PCOS 和子宫内膜异位症)的 1-2 毫升月经血样本。采用 Ficoll-Paque 密度梯度离心法分离 MenSCs,通过流式细胞术进行鉴定。在 20%卵泡液(FF)下诱导 MenSCs,然后通过实时 PCR 和免疫细胞化学检测评估其分化情况。来源于子宫内膜异位症的 MenSCs 的形态与 PCOS 和健康女性不同,但 CD 标志物模式相似。所有诱导的 MenSCs 在培养的第 2 周均表现出形态变化,并表达卵母细胞相关基因(STELLA、GDF9、STRA8、PRDM、LHR、FSHR、SCP3、DDX4 和 ZP2),但各组之间存在显著差异。来源于子宫内膜异位症的 MenSCs 基因和蛋白表达水平均较高。这些发现表明,来源于子宫内膜异位症和 PCOS 患者的 20%FF 诱导的 MenSCs 不仅可以分化为卵母细胞样细胞,而且与健康女性相比具有更高的分化潜能。这表明可以使用患者自身的 MenSCs 分化为卵母细胞样细胞。

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