As with any journey into unchartered territory, the road is still being paved, but significant progress has been made in the past few years in the development of human microphysiological systems (MPS) or "organs-on-chips" systems. This progress is thanks to a collaboration between the National Institutes of Health (NIH), the Defense Advanced Research Projects Agency (DARPA), and the US Food and Drug Administration (FDA) to fund various research projects that promote development MPS. MPS more accurately reflect what happens in our bodies and are, therefore, more physiologically relevant than cell culture and animal models, both of which are routinely used in research today. A major goal of using MPS is to provide a solution to the current drug discovery pipeline problem of only a small fraction of new drugs meeting criteria for approval by the US FDA. Clinical trial failures of new drug therapies are largely attributed to lack of efficacy as well as unidentified toxicities. It is the expectation that organ-on-chip systems, either single organs such as liver for predicting hepatotoxicity, or comprised of multiple organs to predict multi-organ toxicities, will allow for more accurate predictions of drug toxicity. Particularly because inherent species differences in drug metabolizing enzyme activities, as well as cell type specific sensitivities between species will be eliminated.
Dr. Anthony Bahinski from the Wyss Institute at Harvard University presented convincing evidence that lung-on-a-chip models could simulate "breathing-like" contractions, and when challenged with nano particles the toxicity observed was similar to that observed in animal studies with mice. Development of such small-airways-on-a-chip model holds promise for therapies for asthma and COPD disorders. MPS systems for gut, brain and many other organs are under development and the goal is to link them together so that a systems response can be determined.
Dr. Clive Svendsen from Cedars Sanai Medical Center raised the concept of personalized medicine, and being able to study 'disease-on-a-chip' with the system, and eventually being able to study 'patient-on-a-chip.' Another challenge that would be met with MPS is that the majority of US FDA approved drugs don't cross the blood-brain barrier, but with brain-on-a-chip study systems, generated using stem cells, we can get greater understanding about debilitating neuronal disorders.
Dr. John Wikswo from Vanderbilt University believes that with organ-on-chip systems we might finally be able to address the problem in biology that "one cannot understand the whole without understanding the parts, one cannot understand the parts without understanding the whole." The ability to study cells to organs to multi-organs may be the best way to go.
Dr. Yvonne Dragan from DuPont posed the question of "what's the next frontier." The goals are to go from organ-on-chip, to human-on-chip, to population-on-chip. For her, a key step that is still needed in MPS research is demonstration of reliability and predictability using compounds of known toxicities in humans, animals and cell culture models.
Dr. Suzanne Fitzpatrick from the US FDA also thought that as promising as MPS appears to be for advancing biomedical research and drug discovery, there is still a need for validation of MPS as a reliable model for predicting human toxicity. Her perspective is that new methods have to be as good or better than existing ones to allow regulatory agencies to make confident decisions to ensure the safety of the public.
Continuance of collaborative research efforts on MPS is pioneering a way to get back to the whole organism, and it is the expectation that in five years organ-on-chip systems will make significant impact in our ability to predict toxicity, and develop therapeutics that will positively impact our health.
This blog discusses highlights from the SOT Annual Meeting and ToxExpo Workshop Session “ In Vitro Microphysiological Systems--Developing Confidence in Predictive Ability.”