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Design Innovation for Improved Toxicity Testing

Awarded the “Design of the Year” by the London Design Museum in 2015, microphysiological systems or “organs-on-chips” could fundamentally change drug toxicity testing. Despite decades of research using animal and cell models, predicting drug-induced toxicity in humans remains a significant challenge. While animal toxicology studies identify some significant problems, lack of animal toxicity is no guarantee that a drug will be safe in humans. In fact, toxicity remains one of the major reasons for withdrawing an approved drug from the market. Engineering advances have fueled the development of microphysiological systems that mimic human organs most vulnerable to drug toxicity. 

In a CTS commentary, Low and Tagle describe NIH and DARPA funded efforts to develop a panel of “organs-on-a-chip” and the integration of multiple platforms into a “human-on-a-chip”. The field is advancing rapidly, with models for the liver sinusoid, kidney proximal tubule and gut enteroids among those holding great promise for toxicity testing. Integration of gut, liver, kidney, skeletal muscle and blood-brain barrier platforms will permit testing of specific hypotheses regarding multiorgan involvement in drug efficacy and toxicity. However, the true impact of these advances await solutions to significant barriers, including the availability of human cells. The convergence of advances in human induced pluripotent stem cell technology and microfluidics holds promise for addressing this critical limitation. Both NCATS and DARPA should be applauded for their support of these efforts. Cross-pollination of engineers, biologists and pharmacologists fuels the success of “organ-on-a-chip” efforts. Such multidisciplinary approaches hold great promise for the development of more predictive models of human organ toxicity. These systems will also likely serve as scaffolds for modeling disease and for studying population differences in drug efficacy and toxicity.     

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