PERFUSED IN VITRO INTESTINE TISSUE FOR STUDYING INFLAMMATORY BOWEL DISEASE RESPONSE TO DRUG THERAPIES

Abstract

Abstract A dynamic perfusion system was designed for cultivation an in vitro model comprising human intestinal colonoids, intestinal myofibroblasts, and monocyte-derived macrophages. The primary aim was to investigate the effect of therapeutic interventions on inflammatory bowel disease (IBD) using this bioengineered system. The approach involved creating a a colonoid epithelial monolayer on a scaffold lumen with myofibroblasts and macrophages in the subepithelial compartment, which was then integrated into a bioreactor enabling controlled perfusion mimicking the dynamic intestinal microenvironment to introduce inflammation and assess responses to traditional and innovative therapies. Inflammation induction in the model resulted in decreased epithelial integrity along with the upregulation of pro-inflammatory cytokines. The addition of myofibroblasts amplified the secretion of pro-inflammatory cytokines GCP-1, GM-CSF, and IL-1α, while concurrently reducing MCP-1 levels. The introduction of myofibroblasts contributed to an enhanced inflammatory response in the tissue. This system is poised to serve as a valuable tool for evaluating potential therapeutic strategies aimed at addressing IBD.