Abstract

Gut on-a-Chip: Towards a More Predictive and Physiological Human Intestinal Barrier Model

Evita Steeg, Researcher, TNO Quality Of Life

A majority of the preclinical intestinal models do not properly reflect the complex physiology of the human intestinal tract, resulting in low translational value. We have developed the InTESTine model, using fresh ex vivo (human) intestinal tissue mounted into a 2-compartmental microfluidic model with luminal and basolateral flow. Using InTESTine on-a-chip model the human intestinal tissue remains functional for 24 hours during incubations, as presented by proper transport and metabolic functionality and remained barrier integrity, and the model shows additional value in predicting human intestinal absorption of pharmaceuticals and nutrients. Besides ex vivo intestinal tissue, (human) intestinal stem-cell derived organoids possess promising features, especially when cultured as an epithelial monolayer. By applying microfluidic flow we stimulated growth of a confluent epithelial monolayer by showing an increase in TEER, limited vectorial leakage of FD4, while remaining phenotypic properties like cell proliferation and differentiation into the distinct cell types of the intestinal epithelium. In conclusion, we now can successfully use the human intestinal tissue and intestinal organoid monolayers for longer-term incubations, which can be applied as a reliable tool for studying processes that determine human intestinal permeability as well as (anaerobic) host-microbe-immune responses when mounted in the microfluidic device.