Poster #089
Modeling Intestinal Fibrosis Using Stem Cells from Crohn’s Disease Patients
Mentors: Christian Wong-Valenica, PhD; Robert Barrett, PhD
Intestinal fibrosis is a severe complication of Crohn’s disease (CD) characterized by the accumulation of scar tissue in the intestinal wall. Currently, intestinal fibrosis remains poorly understood due to the lack of physiologically relevant models. This study aims to investigate the molecular mechanisms of fibrosis using human intestinal organoids (HIOs) derived from induced pluripotent stem cells (iPSCs) from CD patients. HIOs were separated into epithelial-only HIOs (eHIOs) and mesenchymal populations to research cell-specific responses and then treated with a combination of cytokines to stimulate the fibrotic response. Using qPCR and ELISA, we observed an increased expression of fibrotic related genes in response to treatment. Using fluorescent microscopy, we detected an increase in deposition of extracellular matrix (ECM) proteins from mesenchymal cells. These findings deepen our understanding of the molecular pathogenesis of intestinal fibrosis in CD and provide a robust model for the development of anti-fibrotic therapies.