P864 A microfluidic-based human gut-on-a-chip for 3D organ and disease modelling

Intestinal barrier disruption as a result of pathological states or drug-induced toxicity can lead to life-threatening conditions and cease drug discovery. Current in vitro 2D intestinal models lack the features of the in vivo settings like tubular structure or perfusion and fail in clinical translation. MIMETAS OrganoPlate® technology enables culturing of 3D tube-like structures with a membrane-free ECM boundary and a pump-free perfusion. Here we show human gut-on-a-chip model which is composed of gut epithelial cells grown inside of the microfluidic channel of the OrganoPlate®. We established epithelial barrier model of intestinal tract that develop into a barrier tissue showing rapid cell polarisation, tight junction formation and proper expression of intestinal markers. These gut tubules are suitable for high-throughput toxicity screening, real-time imaging of transport and leakage. For instance, recently we applied the OrganoPlate® platform to develop cytokine-induced IBD CACO2 model suitable for target discovery and validation. Stimulation of gut tubes with proinflammatory cytokines results in disruption of epithelial barrier that can be prevented by treatment with known IBD therapeutics. Culture of these IBD gut tubes in OrganoPlate® allows automated readout of the barrier integrity which is followed by image analysis and quantification. OrganoPlate® technology allows development of complex models to recreate an in vivo metabolic and immunological responses following their co-culture with immune cells and/or bacteria. Moreover, gut-on-a-chip models allow to study inflammatory bowel diseases (IBD) like Crohn’s disease and Ulcerative colitis and support screening for potential drug targets for these diseases. MIMETAS OrganoPlate® technology offers novel ways for studying the organ development and physiology as well as disease mechanisms.