Generation of a three-dimensional collagen scaffold-based model of the human endometrium.

Abstract

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 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 lyophilisation to direct cellular organisation, integrating organoids with primary isolates of stromal cells. The internal pore structure of the scaffold was optimised for stromal cell culture in a systematic study, finding an optimal average pore size of 101 μm. Endometrial organoids (EO) seeded organise to form a luminal-like epithelial layer, on the surface of the scaffold. The cells polarise 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 (ECM) proteins. Both cell types are hormone responsive on the scaffold, with hormone stimulation resulting in epithelial differentiation and stromal decidualization.