Abstract Background Fistulas are a debilitating complication of Crohn’s disease (CD), characterized by abnormal invasive tracts lined with transitional cells undergoing hybrid epithelial-to-mesenchymal transition (EMT)1,2. These cells retain partial epithelial identity while acquiring migratory properties3. The mechanisms driving this hybrid EMT and associated tissue disruption remain poorly defined, due to a lack of physiologically relevant models. We aimed to model fistula-associated EMT using human intestinal organoids (HIOs) derived from both ileal and colonic tissue. Methods HIOs were derived from ileal (healthy n = 4; CD n = 2) and colon (healthy n = 4) biopsies. HIOs were cultured in 50% Matrigel with 8-day CD fistula-enriched cytokine treatment of TGFβ, TNFα, IL-13 14(11):1514-1527. https://doi.org/10.1002/ibd.20590. 2.Scharl M, Frei S, Pesch T, et al. Interleukin-13 and transforming growth factor β synergise in the pathogenesis of human intestinal fistulae. Gut. 2012;62(1):63-72. https://doi.org/10.1136/gutjnl-2011-300498 3.Georgette C, Tandon R, Simmons A. Pathogenesis of Fistulating Crohn’s Disease: A Review. Cellular and Molecular Gastroenterology and Hepatology. 2022;15(1):1-11. https://doi.org/10.1016/j.jcmgh.2022.09.011 Conflict of interest: Ms. Kola-Ilesanmi, Darasimi: No conflict of interest Stephens, Matthew: No conflict of interest Thorne, Andrew: No conflict of interest Mackenzie, Colin: No conflict of interest Mcdonald, Braedon: No conflict of interest Visser, Frank: No conflict of interest Hirota, Simon: Consultant with Access Nutrients
Kola-Ilesanmi et al. (Thu,) studied this question.
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