Abbas Yassen, Brunel Lucia G, Hollinshead Michael S, Fernando Ridma C, Gardner Lucy, Duncan Imogen, Moffett Ashley, Best Serena, Turco Margherita Y, Burton Graham J, Cameron Ruth E
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Centre for Trophoblast Research (CTR), University of Cambridge, Cambridge CB2 3EG, UK.
Interface Focus. 2020 Apr 6;10(2):20190079. doi: 10.1098/rsfs.2019.0079. Epub 2020 Feb 14.
The endometrium is the secretory lining of the uterus that undergoes dynamic changes throughout the menstrual cycle in preparation for implantation and a pregnancy. Recently, endometrial organoids (EO) were established to study the glandular epithelium. We have built upon this advance and developed a multi-cellular model containing both endometrial stromal and epithelial cells. We use porous collagen scaffolds produced with controlled lyophilization to direct cellular organization, integrating organoids with primary isolates of stromal cells. The internal pore structure of the scaffold was optimized for stromal cell culture in a systematic study, finding an optimal average pore size of 101 µm. EO seeded organize to form a luminal-like epithelial layer, on the surface of the scaffold. The cells polarize with their apical surface carrying microvilli and cilia that face the pore cavities and their basal surface attaching to the scaffold with the formation of extracellular matrix proteins. Both cell types are hormone responsive on the scaffold, with hormone stimulation resulting in epithelial differentiation and stromal decidualization.
子宫内膜是子宫的分泌性内膜，在整个月经周期中会发生动态变化，为着床和怀孕做准备。最近，人们建立了子宫内膜类器官（EO）来研究腺上皮。我们在此基础上更进一步，开发了一种包含子宫内膜基质细胞和上皮细胞的多细胞模型。我们使用通过可控冻干法生产的多孔胶原支架来引导细胞组织，将类器官与基质细胞的原代分离物整合在一起。在一项系统性研究中，对支架的内部孔隙结构进行了优化以用于基质细胞培养，发现最佳平均孔径为101 µm。接种的EO会组织起来，在支架表面形成类似管腔的上皮层。细胞发生极化，其顶端表面带有微绒毛和纤毛，朝向孔隙腔，而其基底表面通过形成细胞外基质蛋白附着在支架上。两种细胞类型在支架上都对激素有反应，激素刺激会导致上皮分化和基质蜕膜化。
