Gut-liver interaction study on an all-polydimethylsiloxane microfluidic device integrating intestinal paracellular permeability assay

Abstract

Microphysiological systems (MPSs) have attracted increasing attention as a method for simulating in vitro drug efficiency. In particular, the interaction between liver and intestine tissues is one of the primary targets since they are closely involved in drug absorption and metabolism. However, most of the intestine-liver MPSs reported previously require pumps, electrodes, and porous membranes for co-culture of cells and evaluation of intestinal permeability (i.e., Trans-Epithelial Electrical Resistance, TEER), requiring complex manufacturing processes and operations. In this study, we report an all-polydimethylsiloxane (PDMS) co-culture microfluidic device, connecting microchamber-based paracellular transport assay on gut microtissues to liver tissues matured on the same device. On one side of the device, HepaRG cells are confined within thin parallel grooves that induce their differentiation into hepatocytes. The other side of the device is connected with microchannels to the liver side and includes the gut tissues, organized above microchambers. Such microchambers allow the evaluation of paracellular permeability by fluorescence imaging. Thanks to the microfluidic device we investigated changes in intestinal permeability induced by differentiated hepatocyte excretion and found that Caco-2 permeability was decreased when co-culture with HepaRG. Due to its simplicity and straightforward implementation, this method is anticipated as an innovative and efficient approach to assess tissue barrier function in multi-organ on-chip experiments.