A Versatile Intestine‐on‐Chip System for Deciphering the Immunopathogenesis of Inflammatory Bowel Disease

Abstract

The multifactorial nature of inflammatory bowel disease (IBD) necessitates reliable and practical experimental models to elucidate its etiology and pathogenesis. To model the intestinal microenvironment at the onset of IBD in vitro, it is important to incorporate relevant cellular and non‐cellular components before inducing stepwise pathogenic developments. We present a novel intestine‐on‐chip system for investigating multiple aspects of IBD's immunopathogenesis. The system includes an array of tight and polarized barrier models formed from intestinal epithelial cells on an in‐vivo‐like subepithelial matrix within one week. The dynamic remodeling of the subepithelial matrix by cells or their secretome demonstrated the physiological relevance of the on‐chip barrier models. The system design enabled introduction of various immune cell types and inflammatory stimuli at specific locations in the same barrier model, which facilitated investigations of the distinct roles of each cell type in intestinal inflammation development. We showed that inflammatory behavior manifested in an upregulated expression of inflammatory markers and cytokines (TNF‐α). The neutralizing effect of the anti‐inflammatory antibody Infliximab on levels of TNF‐α and its inducible cytokines could be explicitly shown. Overall, we present an innovative approach to systematically developing a microphysiological system to comprehend immune‐system‐mediated disorders of IBD and to identify new therapeutic strategies .

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