A "living biobank" of Crohn's Disease

Patient-derived organoids (PDOs) from the colons of patients with Crohn's Disease (or healthy controls) were subjected to in-depth genotype, transcriptome and phenotype assessment. These studies revealed that CD may be classified broadly into two molecular subtypes, each with its unique profile of dysregulated celluar processes. We further show that these phenotypes can be rectified with matched therapeutics, hence making such intervention personalized. Findings show that CD-PDOs could serve as pre-clinical platforms for drug discovery and personalized medicine. Patients representing various subtypes of Crohn's disease (CD) [Montreal classification-B1/2/3, perianal] were enrolled into this study to obtain tissue biopsies which would serve as source of adult stem cells for the generation of patient-derived organoids (PDOs). Standard cell biological, biochemical, functional and phenotypic assays were used to assess the PDOs for: 1) barrier integrity, 2) apoptosis, 3) proliferation, 4) ROS induced DNA/RNA damage; 5) senescence and DNA damage; 6) bacterial clearance, 7) induction of inflammatory cytokines, and morphology/growth characteristics. Please note that the cell biological, biochemical, and functional assays are not done on these GEO samples prior to RNA analysis, but characterization that is independent of the samples sequenced. The current records are the content of the associated manuscript to validate RNA seq findings.