Organs-on-chips (microphysiological systems): tools to expedite efficacy and toxicity testing in human tissue

Although basic scientific research has generated methodological and technical innovations rapidly in recent decades, translational science has not kept pace. Among the factors contributing to the slower pace of translation is a bottleneck in the drug discovery pipeline. This is due in part to the widespread failure of therapeutics in early phase clinical trials, despite promising results from preclinical testing. Improved tools that better predict adverse effects in humans for therapeutics are much needed to reduce the rate of failed trials. Safety, toxicity and efficacy assessment using human tissue as a supplement to animal models prior to clinical testing in humans could reduce clinical trial failure rates, leading to significant savings in lives, time and money. The Microphysiological Systems (MPS) Program (‘‘organs-on-chips’’) (http://www.ncats.nih.gov/research/ reengineering/tissue-chip/tissue-chip.html) supports an innovative approach to preclinical toxicity testing on human tissue: development of in vitro, three-dimensional organ systems from human cells on bioengineered platforms that mimic in vivo tissue architecture and physiological conditions in order to facilitate and accurately monitor key organ-level functions. The platforms incorporate complex factors found in vivo, including extracellular scaffolding, three-dimensional structure, cellular interactions (including between different cell types), perfusion, biomechanical stresses (e.g., stretch and shear forces from fluid flow), electrical stimulation of excitable tissue, hormone responses, etc. These features are present in animal models, but some aspects of animal physiology do not accurately represent those of humans. Development of human organ microsystems to bridge the gap between preclinical testing in animals and human clinical trials would be a significant advancement.