Porcine intestinal organoids cultured in an organ-on-a-chip microphysiological system

Preclinical studies are a vital component of pharmaceutical development and improvements in the predictive value of in vitro studies are essential. Organ-on-a-chip in vitro models are a recent advancement in the pursuit of improved reproduction of in vivo tissue complexity. Here, we report the development and characterization of porcine intestinal cells from organoids on chips with microfluid dynamics and peristaltic-like strain in a microphysiological system. Intestinal epithelial cells were grown on a porous membrane as a co-culture with human intestinal microvascular endothelial cells for up to 12 days. These cultures formed villi-like structures and established a tight barrier replete with F-actin and tight junctions. A demarcated region of the epithelial cells was in an actively proliferative stage, reminiscent of intestinal crypts. The intestinal epithelial cell growth was characterized for the presence of enterocytes, goblet cells and enteroendocrine cells. Notable drug transporters and CYP450 metabolic activity were present in these cultures. The organoid chip maintained barrier function as the paracellular permeability was low. In contrast, the permeability enhancer, sodium caprate (C₁₀), increased the apparent permeability of molecular weight marker compounds by 2- to 3-fold, and upon removal of C₁₀, the barrier was shown to be recovered. The porcine intestinal chip represents a new in vitro model with potential application in multiple aspects of pharmaceutical testing including drug metabolism, drug transporters and safety.