(151a) Human In Vitro Models to Improve Preclinical Testing of Drugs

Human microphysiological or “Body-on-a-Chip” systems are powerful tools to assess the potential efficacy and toxicity of drugs in pre-clinical studies. Having a human based, multiorgan system, that emulates key aspects of human physiology can provide important insights to complement animal studies in the decision about which drugs to move into clinical trials. Our human surrogates are constructed using a low cost, robust “pumpless” platform. We use this platform in conjunction with “functional” measurements of electrical and mechanical activity of tissue constructs. Using a system with four or more organs we can predict the exchange of metabolites between organ compartments in response to various drugs and dose levels. We have constructed models incorporating barrier tissues such as GI tract, blood brain barrier, and skin with internal organs such as liver, cardiac, and neuromuscular junctions. We will provide examples of using the system to both predict the response of a target tissue as well as off target responses in other tissues/organs. We believe such models will allow improved predictions of human clinical response from preclinical studies.