Human colon or ileum organoid models for inflammatory bowel disease (IBD) research

Intestine

Principal Investigators

• Prof. Séverine Vermeire, MD, PhDa,b
• severine.vermeire@uzleuven.be
• Department of Gastroenterology and Hepatology, University Hospitals Leuven
• Prof. Bram Verstockt, MD, PhDa,b
• bram.verstockt@uzleuven.be
• Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven
• https://www.ibd-leuven.com/

3D tissue models & origin

• Organoids generated from human colon or ileum (healthy, ulcerative colitis, Crohn’s disease) \
• Organoid-derived 2D monolayer for barrier permeability assays
• Co-culturing of microbiota from healthy or IBD donors with matching organoid-derived 2D monolayer
• Gut-on-a-chip (Emulate platform) to include peristalsis-like stretching motions with co-culture models (epithelium, endothelium, immune cells, microbiota)

Method description:

Organoid-derived 2D monolayer: they are generated from healthy or diseased intestinal organoids, and used to easily evaluate barrier permeability via TEER or FITC-dextran measurements.

Co-culturing: microbiota from healthy or IBD donors can be co-cultured on organoid-derived 2D monolayer to understand how its different composition might affect the intestinal epithelium. Human intestinal microvascular endothelial cells and patient-derived PBMCs can be co-cultured on gut-on-a chips (see below) to better mimic the in-vivo situation.

Gut-on-a-chip: the seeding of intestinal organoids on chips from Emulate, Inc. enable us to model more complex human physiology and disease. Besides the ability to establish more complex co-cultures by integrating additional cell types, these chips can be subjected to peristalsis-like stretching motions

Imaging: Histochemical and immunofluorescence stained intestinal organoids are imaged using different microscopy systems (NLO, etc.) to identify morphological clues and spatially localize specific proteins in the epithelium.

Assay development: all the previous technologies are used for the development of assays for pre-clinical drug screening and precision medicine approaches.

Illustrations

Patient-derived intestinal organoids:

Application

• Pre-clinical drug screening
• Precision medicine
• IBD disease modelling

Some key publications

• Noben M, Verstockt B, de Bruyn M, et alEpithelial organoid cultures from patients with ulcerative colitis and Crohn's disease: a truly long-term model to study the molecular basis for inflammatory bowel disease? Gut 2017;66:2193-2195. 10.1136/gutjnl-2016-313667
• Vanhove W, Nys K, Arijs I, et al. Biopsy-derived Intestinal Epithelial Cell Cultures for Pathway-based Stratification of Patients With Inflammatory Bowel Disease. J Crohns Colitis 2018;12(2):178-187. 10.1093/ecco-jcc/jjx122
• Vancamelbeke M, Laeremans T, Vanhove W, et al. Butyrate Does Not Protect Against Inflammation-induced Loss of Epithelial Barrier Function and Cytokine Production in Primary Cell Monolayers From Patients With Ulcerative Colitis. J Crohns Colitis 2019;13(10):1351-1361. 10.1093/ecco-jcc/jjz064
• Arnauts K, Verstockt B, Ramalho AS, Vermeire S, Verfaillie C, Ferrante M. Ex Vivo Mimicking of Inflammation in Organoids Derived From Patients With Ulcerative Colitis. Gastroenterology 2020;159(4):1564-1567. 10.1053/j.gastro.2020.05.064
• Arnauts K, Sudhakar P, Verstockt S, et al. Microbiota, not host origin drives ex vivo intestinal epithelial responses. Gut Microbes 2022;14(1):2089003. 10.1080/19490976.2022.2089003

Contact person:

1. Prof. Séverine Vermeire,
   • severine.vermeire@uzleuven.be
2. Prof. Bram Verstockt,
   • bram.verstockt@uzleuven.be