Abstract

Immunocompetent Gut-on-a-Chip as a Model of Tissue Inflammation

Nikolce Gjorevski, Scientist, Mechanistic Safety, Pharmaceutical Sciences, Roche Pharmaceutical Research and Early Development

Owing to its complex and multifactorial nature, inflammatory bowel disease (IBD) remains poorly understood, which, in turn, renders the development of effective IBD therapies a major challenge. The poor translatability of IBD therapeutics from mice to humans may be attributed in large part to the fundamental immunological differences between the two species. Advanced three-dimensional (3D) culture models and microphysiological systems are emerging as superior alternatives to animals in capturing human-specific physiology and disease. We have created an immune-competent gut-on-a-chip model comprising a tight intestinal epithelial barrier, extracellular matrix, resident and circulating immune cells. Beyond a mere co-culture, the system recapitulates the crucial multidirectional interactions between matrix, parenchymal and immune cells that generate an inflammatory milieu and ultimately result in epithelial damage in the context of IBD. The physiological completeness of the model may help afford fundamental insight into the mechanisms that drive chronic inflammation in the gut and other organs, ultimately supporting drug discovery.