Cochin Institute, Inserm UMR 1016, CNRS 8104, Université Paris Descartes, 24 rue du faubourg St Jacques, 75014, Paris, France.
Imagine Institute, Inserm UMR 1163, CNRS ERL 8254, Université Paris Descartes-Sorbonne Paris Cité, Paris, France.
Reprod Sci. 2020 Aug;27(8):1627-1636. doi: 10.1007/s43032-020-00193-8.
Thoracic endometriosis (TE) syndrome is a clinical condition known as an extrapelvic form of endometriosis with the presence of functioning endometrial tissue involving lung parenchyma, pleura, chest wall, or diaphragm. In an effort to obtain an endometriosis ex vivo model, we established the spontaneously growing TH-EM1 cell line from endometriotic implants in lung parenchyma from a woman with TE. Maintained in long-term culture, the cells grew as large mesenchymal-like cells with a doubling time between 5 and 6 days. Treatment with medroxyprogesterone acetate (10 mol/L) inhibited the TH-EM1 cells growth and induced morphological changes to an epithelial-like cells. Strong expression of the nuclear estrogen receptors, progesterone receptors, and erytropoietin receptors were found in both the pulmonary implant and the TH-EM1 cells by immunohistochemical analysis. Consistent immunoreactivity of TH-EM1 cells for CD9, CD13, CD73, CD90, CD105, and CD157 was revealed by flow cytometry. Likewise, the embryonic markers, SRY-box 2 (SOX-2) and the Nanog molecules, were detected in 76% and 52% of the cells, while fetal hemoglobin and a-globin were detected in 76% and 65% of TH-EM1 cells, respectively. By RHG banding, normal metaphases were observed, while the microarray chromosomal analysis showed gains of DNA sequences located on the segments 8p23.1, 11p15.5, and 12p11.23. The described in vitro cellular model can serve as a useful tool to study the pathogenesis of endometriosis and to improve the knowledge of molecular mechanisms controlling the endometriotic cell dissemination potential.
胸腔子宫内膜异位症 (TE) 综合征是一种已知的盆腔外子宫内膜异位症形式,其特征是肺实质、胸膜、胸壁或膈肌存在功能子宫内膜组织。为了获得子宫内膜异位症的体外模型,我们从患有 TE 的女性的肺实质内的子宫内膜异位症种植体中建立了自发生长的 TH-EM1 细胞系。在长期培养中,这些细胞生长为具有间充质样特征的大型细胞,倍增时间为 5-6 天。用醋酸甲羟孕酮 (10 mol/L) 处理可抑制 TH-EM1 细胞生长并诱导其向上皮样细胞形态发生变化。免疫组织化学分析显示,肺种植体和 TH-EM1 细胞中均强烈表达核雌激素受体、孕激素受体和促红细胞生成素受体。通过流式细胞术发现 TH-EM1 细胞对 CD9、CD13、CD73、CD90、CD105 和 CD157 的免疫反应性一致。同样,胚胎标记物 SOX-2 和 Nanog 分子在 76%和 52%的细胞中被检测到,而胎儿血红蛋白和 a-球蛋白分别在 76%和 65%的 TH-EM1 细胞中被检测到。通过 RHG 带型观察到正常中期,而微阵列染色体分析显示 DNA 序列增益位于 8p23.1、11p15.5 和 12p11.23 片段上。所描述的体外细胞模型可作为研究子宫内膜异位症发病机制和提高控制子宫内膜异位症细胞扩散潜力的分子机制知识的有用工具。