Abstract

Building a Human Body on a Chip: An Ongoing Journey 1989-20?? — A 33-year Odyssey

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

A physiologically representative, multiorgan microphysiological system (or MPS) based on human tissues may become a transformative technology to improve selection of drug candidates most likely to earn regulatory approval from clinical trials. Also, such systems can be used to test cosmetics, food ingredients, and chemicals for potential toxicity. In this talk we will explore the history of the development one type of MPS known as a "Body-on-a-Chip" as well as current and future elaborations of this technology. Current "Body-on-a-Chip" systems combine organized tissue/organ mimics with the techniques of microfabrication based on PBPK (Physiologically Based Pharmacokinetic) models. Currently these systems are "self-contained" and do require external pumps, leading to "pumpless systems" which eliminates the need for an external pump, reduces system cost and improves operational reliability. While the fluid (or blood surrogate) in these systems can be sampled directly to allow measurement of concentrations of drug, metabolites or biomarkers, they can also be interrogated in situ to determine functional responses such as electrical response, force generation, or barrier integrity. The blood surrogate can be made to be as a serum-free, chemically defined medium facilitating interpretations of responses that are more mechanistic than with serum containing media. A key advantage of this approach is that we can predict both human efficacy and toxicity of a drug or drug combination in preclinical trails, A Hesperos system has been used as the sole source of efficacy data for an IND application by Sanofi for a drug currently in a Phase 2 clinical trial and data from an Emulate system has also been used to support an IND.  For these systems to fulfill their real potential in drug development such use of these systems must become routine.  Further there are questions on human toxicity of cosmetics and other chemicals, particularly mixtures, that can be addressed with such systems.