What question did this study set out to answer?

The aim is to model fistula-associated hybrid EMT using human intestinal organoids derived from Crohn’s disease and healthy tissues.

January 23, 2026

P0075Human intestinal organoids recapitulate fistula-associated hybrid epithelial-to-mesenchymal transition (EMT): A model of Crohn’s disease fistula formation

Key Points

The aim is to model fistula-associated hybrid EMT using human intestinal organoids derived from Crohn’s disease and healthy tissues.
Cultured human intestinal organoids from biopsies of ileal and colonic tissues in Matrigel.
Treated organoids with cytokines related to Crohn's disease fistula formation.
Conducted morphometric analysis and assessed gene/protein expression using RT-qPCR and Western blot.
Cytokine stimulation induced hybrid EMT, transforming organoids into migrating sheets.
Treatment with Upadacitinib reduced EMT features in colon organoids, enhancing circularity.
Significant gene upregulation of SNAI2 and other EMT markers was observed in both ileal and colonic organoids.

Abstract

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

Bookmark

P0075Human intestinal organoids recapitulate fistula-associated hybrid epithelial-to-mesenchymal transition (EMT): A model of Crohn’s disease fistula formation

Key Points

Abstract

Cite This Study