Perfused In Vitro\nIntestine Tissue Model to Evaluate\nthe Role of Stromal and Immune Cells in Epithelial Response to Inflammatory\nCues and Drug Therapies

We establish an in vitro perfusion intestinal tissue\nbioreactor\nsystem tailored to study drug responses related to inflammatory bowel\ndisease (IBD). The system includes key components including multiple\nhuman intestinal cell types (colonoids, myofibroblasts, and macrophages),\na three-dimensional (3D) intestinal architecture, and fluid flow.\nInclusion of myofibroblasts resulted in increased secretion of cytokines\nsuch as glypican-1 (GCP-1), granulocyte-macrophage colony-stimulating\nfactor (GM-CSF), and interleukin 1-α (IL-1α), whereas\ninclusion of macrophages resulted in increased secretion of monocyte\nchemoattractant proteins (MCPs) demonstrating a significant role of\nboth stromal and immune cell types in intestinal inflammation. The\nsystem is responsive to drug treatments, as reflected in the reduction\nof pro-inflammatory cytokine production in tissue in some treatment\nscenarios. While future studies are needed to evaluate more nuanced\nresponses in an IBD context, the present study demonstrates the ability\nto establish a 3D intestinal model with multiple relevant cell types\nand flow that is responsive to both inflammatory cues and various\ndrug treatment options.