Harnessing cell-mediated matrix remodelling by human iPSC-derived intestinal organoids within 3D materials to understand epithelial-mesenchymal interactions in health and disease

Eileen Gentleman (primary)
Centre for Craniofacial and Regenerative Biology
King's College London
Andrew Stagg (secondary)
Centre for Immunobiology, Blizard Institute
Queen Mary University of London


Inflammatory Bowel Disease (IBD) causes chronic intestinal inflammation; however, one of the hallmarks of IBD is pathological matrix remodeling of the intestinal wall, which manifests as either intestinal stricturing (fibrosis) or fistulae formation (degradation). This project uses a combination of modifiable, synthetic 3D matrices and human iPSC-derived intestinal organoids, which contain both epithelial and mesenchymal cells to create a reductionist model of the intestine. Our goal is to fundamentally understand how pathological matrix remodeling in the mesenchyme contributes to inflammatory-like phenotypes in the epithelium, potentially leading to the discovery of targets that could be exploited therapeutically.


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Ferreira SA, Faull PA, Seymour A, Yu TTL, Loaiza S, Auner HW, Snijders AP, Gentleman E (2018) “Neighboring cells override 3D hydrogel matrix cues to drive human MSC quiescence.” Biomaterials. 176:13-23. doi: 10.1016/j.biomaterials.2018.05.032

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Giles EM, Sanders TJ, McCarthy NE, Lung J, Pathak M, MacDonald TT, Lindsay JO, Stagg AJ. Regulation of human intestinal T-cell responses by type 1 interferon-STAT1 signaling is disrupted in inflammatory bowel disease. Mucosal Immunology. 2017 Jan;10(1):184-193. doi: 10.1038/mi.2016.44

Molecules, cells and industrial biotechnology
Area of Biology
BiotechnologyCell Biology
Techniques & Approaches
ChemistryEngineeringImage ProcessingMicroscopy / ElectrophysiologyMolecular Biology