Authors

Discussion

The study of the intestinal epithelial barrier is hampered by the lack of a suitable in vitro model system. Patient-derived organoids (PDOs) recapitulate the cellular diversity and patient heterogeneity and provide a relevant platform to study the intestinal epithelium and its response to microbial or inflammatory challenges.

Here, we present the characterization of an inflammatory bowel disease (IBD) organoid biobank derived from Crohn’s disease and Ulcerative colitis patients and its application for IBD drug development efforts.

PDOs from different regions of the gastrointestinal tract of 14 IBD patients were established. To recapitulate the full cellular diversity, specialized medium formulations were defined that support the differentiation of distinct epithelial cell lineages as confirmed by transcriptional profiles and histology.

To study the inflammation driven loss of barrier integrity observed in the mucosa of IBD patients, we employed organoid derived monolayers and mimicked the inflammatory environment by cytokine challenge (TNF, IFNγ). The cytokine challenge robustly induces loss of barrier integrity across seven patient-derived monolayers. The barrier breakdown was ameliorated in all models by treatment with the IBD therapy Tofacitinib, demonstrating the suitability of the assay for IBD drug development efforts.