Generation of a three-dimensional collagen scaffold-based model of the human endometrium.
Hollinshead, Michael S
Fernando, Ridma C
Turco, Margherita Y
Burton, Graham J
Cameron, Ruth E
The Royal Society
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Abbas, Y., Brunel, L. G., Hollinshead, M. S., Fernando, R. C., Gardner, L., Duncan, I., Moffett, A., et al. (2020). Generation of a three-dimensional collagen scaffold-based model of the human endometrium.. Interface Focus, 10 (2), 20190079. https://doi.org/10.1098/rsfs.2019.0079
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.
funding This work was supported by the Centre for Trophoblast Research and the Wellcome Trust (090108/Z/09/Z, 085992/Z/08/Z); Y.A was supported by an Isaac Newton grant awarded to M.Y.T; L.G.B. was funded by a Marshall Scholarship from the Marshall Aid Commemoration Commission; M.Y.T. is supported by a Royal Society Dorothy Hodgkin Fellowship; S.M.B. and R.E.C. acknowledge funding from EPSRC Established Career Fellowship Grant No. EP/N019938/1.
Royal Society (DH160216)
Wellcome Trust (085992/Z/08/Z)
Wellcome Trust (090108/Z/09/Z)
Engineering and Physical Sciences Research Council (EP/N019938/1)
External DOI: https://doi.org/10.1098/rsfs.2019.0079
This record's URL: https://www.repository.cam.ac.uk/handle/1810/298898
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