P011 Patient-derived organoids as an epithelial model for preclinical IBD research and drug development

Abstract Background The study of the intestinal epithelial barrier is hampered by lack a suitable in vitro model system. Patient-derived organoids (PDOs) recapitulate cellular diversity and patient heterogeneity provide relevant platform to epithelium its response microbial or inflammatory challenges. Here, we present characterization an bowel disease (IBD) organoid biobank derived from Crohn’s Ulcerative Colitis patients application for IBD drug development efforts. Methods PDOs different regions gastrointestinal tract 14 were established. To full diversity, specialized medium formulations defined that support differentiation distinct cell lineages as confirmed transcriptional profiles histology. inflammation driven loss integrity observed mucosa patients, employed monolayers mimicked environment cytokine challenge (TNF, IFNγ). Results In media, displayed gene expression patterns consistent with maturation types found human gut. robustly induces across seven patient-derived monolayers. breakdown was ameliorated all models treatment therapy Tofacitinib. Conclusion Intestinal generated capable differentiate into mature types. PDO-derived built trans-epithelial electrical resistance (TEER) are function mediated breakdown. Proof-of-concept studies Tofacitinib demonstrated suitability assay