Abstract

Organs-on-Chips Technology: Applications in Safety Testing for Drug Discovery and Development

Kyung-Jin Jang, Vice President, Emulate, Inc.

Preclinical animal models used to support selection of drug candidates for clinical trials can sometimes fail to predict potential human toxicity. This translation gap in safety data contributes to drug failures and attrition rates in the clinic. Here, we highlight the application of our microengineered Liver-Chip containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow for toxicity and safety assessment. We showed that our Liver-Chip detected diverse phenotypes of liver toxicity including hepatocellular injury, steatosis, cholestasis, and fibrosis as well as species-specific toxicities when treated with tool compounds.  The adoption of Organs-on-Chips technology in the pharmaceutical industry may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.