Organs-on-Chips As Bridges for Predictive Toxicology

Abstract The next generation of chemical toxicity testing will use organs-on-chips (OoCs)—3D cultures of heterotypic cells with appropriate extracellular matrices to better approximate the in vivo cellular microenvironment. Researchers are already working to validate whether OoCs are predictive of toxicity in humans. Here, we review two other key aspects of how OoCs may advance predictive toxicology—each taking advantage of OoCs as systems of intermediate complexity that remain experimentally accessible. First, the intermediate complexity of OoCs will help elucidate the scale(s) of organismal complexity that currently confound computational predictions of in vivo toxicity from in vitro data sets. Identifying the strongest confounding factors will help researchers improve the computational models underlying such predictions. Second, the experimental accessibility of OoCs will allow researchers to analyze chemical-exposure responses in OoCs using an array of high-content readouts—from fluorescent biosensors...