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.
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