Abstract

Quantitative Assessment of Tissue Chip Technologies

Murat Cirit, Director of Translational Center of Tissue Chip Technologies, Massachusetts Institute of Technology (MIT)

Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm. Success will require quantitative characterization of MPSs and mechanistic analysis of experimental findings sufficient to translate resulting insights from in vitro to in vivo. We describe a systems pharmacology perspective on this problem, incorporating more mechanistic detail than traditional pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) models yet within broadly comprehensive scope. These Systems Pharmacology approaches offer new insight into design of experiments, data interpretation and organ-specific responses, which can be translated to in vivo responses, such as patient-to-patient variability, drug efficacy and toxicity. For example, ADME, pharmacodynamic and toxicodynamic properties of a drug can be experimentally investigated in multi-MPS platforms under various physiological conditions. Complex experimental results can be interpreted using mechanistic pharmacokinetic & pharmacodynamics (PK/PD) models allowing us to predict clinical outcomes more accurately than existing preclinical animal models.