Novel three-dimensional in vitro models of ovarian endometriosis.
Novel three-dimensional in vitro models of ovarian endometriosis.
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DOI：
10.1186/1757-2215-7-17
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发表时间：
2014-02-06
影响因子：
4
通讯作者：
Lawrenson K
中科院分区：
文献类型：
--
作者：
Brueggmann D;Templeman C;Starzinski-Powitz A;Rao NP;Gayther SA;Lawrenson K
子宫内膜异位症的特点是子宫腔外存在功能性子宫内膜组织。十分之一的育龄妇女受到影响。这种慢性疾病通常会导致盆腔疼痛、痛经、不孕症和上皮性卵巢癌风险升高等后果。尽管子宫内膜异位症的流行及其对女性生活的影响，但用于研究复杂疾病生物学、病理生理学和用于临床前新疗法开发的体外和体内模型相对较少。本研究的目的是建立一种新的卵巢子宫内膜异位症的三维（3D）细胞培养模型，并测试它是否比传统的二维（2D）单层培养更能反映子宫内膜异位症生物学。一株新型卵巢子宫内膜异位症上皮细胞系（EEC16）分离自34岁重度子宫内膜异位症女性。在使用体外实验、western blotting和rna测序对细胞进行表征后，该细胞系和另一种已经很好表征的子宫内膜异位症细胞系EEC12Z被建立为体外3D球体模型。我们使用免疫组织化学和实时半定量PCR比较了三维球体与二维培养物和人子宫内膜异位症病变的生物学特征。与正常卵巢上皮细胞相比，EEC16在体外实验中表现出肿瘤转化的特征。在3D培养下，EEC16和EEC12Z与2D单层培养相比，显示出子宫内膜异位症相关基因的差异表达，更接近于模拟人类子宫内膜异位症病变的分子和组织学特征。据我们所知，这是子宫内膜异位症体外球形模型的首次报道。3D子宫内膜异位症模型为研究EEC生物学和开发新的治疗方法提供了有价值的实验工具。
Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity. It affects 1 in 10 women of reproductive age. This chronic condition commonly leads to consequences such as pelvic pain, dysmenorrhea, infertility and an elevated risk of epithelial ovarian cancer. Despite the prevalence of endometriosis and its impact on women’s lives, there are relatively few in vitro and in vivo models available for studying the complex disease biology, pathophysiology, and for use in the preclinical development of novel therapies. The goal of this study was to develop a novel three-dimensional (3D) cell culture model of ovarian endometriosis and to test whether it is more reflective of endometriosis biology than traditional two dimensional (2D) monolayer cultures. A novel ovarian endometriosis epithelial cell line (EEC16) was isolated from a 34-year old female with severe endometriosis. After characterization of cells using in vitro assays, western blotting and RNA-sequencing, this cell line and a second, already well characterized endometriosis cell line, EEC12Z, were established as in vitro 3D spheroid models. We compared biological features of 3D spheroids to 2D cultures and human endometriosis lesions using immunohistochemistry and real-time semi-quantitative PCR. In comparison to normal ovarian epithelial cells, EEC16 displayed features of neoplastic transformation in in vitro assays. When cultured in 3D, EEC16 and EEC12Z showed differential expression of endometriosis-associated genes compared to 2D monolayer cultures, and more closely mimicked the molecular and histological features of human endometriosis lesions. To our knowledge, this represents the first report of an in vitro spheroid model of endometriosis. 3D endometriosis models represent valuable experimental tools for studying EEC biology and the development of novel therapeutic approaches.
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影响因子：
64.8
作者：
HAO, Y;CRENSHAW, T;TYCKO, B
通讯作者：
TYCKO, B
影响因子：
8.5
作者：
Lawrenson, K.;Benjamin, E.;Dafou, D.
通讯作者：
Dafou, D.
影响因子：
64.8
作者：
FERGUSONSMITH, AC;SASAKI, H;SURANI, MA
通讯作者：
SURANI, MA
DOI：
10.1016/s0889-8545(05)70302-8
发表时间：
1997-06-01
影响因子：
3.2
作者：
Eskenazi, B;Warner, ML
通讯作者：
Warner, ML
影响因子：
5
作者：
Li, NFF;Wilbanks, G;Gayther, SA
通讯作者：
Gayther, SA