Abstract

Human In Vitro Models to Improve Preclinical Testing of Drugs

Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University; President Hesperos, Inc.

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 and in vitro studies using human cells from a single organ in the decision about which drugs to move into clinical trials1.  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 (in collaboration with J. Hickman, University of Central Florida). Also by combining PBPK-PD models2 with these devices we can enhance our predictive power for anticipating human responses. 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. With these systems, we can predict both efficacy and toxicity of drugs in humans from preclinical studies3.  Further, we can use these systems to investigate temporal concentration relationships of drugs during preclinical development4. We believe that these “Body-on-a-Chip” systems have great potential to increase the efficiency of conversion of drug candidates into successful projects.