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.
|
|
