Liver Microphysiological System for Drug-Induced Liver Injury (DILI) Evaluation Based on Kinetic Pump Integrated Microfluidic Plate (KIM-Plate)

Abstract

Prediction of the risk of developing Drug-induced liver injury (DILI) is very important in drug discovery. Although animal tests usually evaluate DILI, the prediction accuracy of DILI is low because experimental animals have different metabolic pathways from humans. A few microphysiological systems (MPS) have been developed as novel evaluation systems for DILI evaluation. However, the proposed system is not yet practical due to operability, throughput issues, and prediction accuracy. Our purpose is to develop a practical DILI evaluation system. In this study, we investigate the influence of perfusion culture on hepatotoxicity tests using our previously developed Kinetic pump integrated microfluidic plate (KIM-Plate). The results of acetaminophen toxicity tests showed that perfusion culture using KIM-Plate improved the detection sensitivity of hepatotoxicity. We suggest that the liver model MPS based on KIM-Plate could be a novel DILI evaluation system that integrates highly functional liver models and coculture with immune cells.