Human-on-a-Chip Systems for Concurrent Toxicity and Efficacy Evaluation for Pre-Clinical Applications
James Hickman,
Professor,
University of Central Florida
The utilization of human-on-a-chip or body-on-a-chip systems for toxicology and efficacy that ultimately should lead to personalized medicine has been a topic that has received much attention recently. Currently drug discovery and subsequent regulatory approval for new candidates requires 10-15 years of development time before general availability is granted by either the FDA or EMA. This can be at either the single organ level, or more importantly, advanced systems where multiple organ mimics are integrated in a serum-free defined medium under flow to allow organ to organ communication and interactions for mechanistic investigations for not only safety but efficacy as well. The idea is to integrate BioMEMs devices and surface modifications with protein and cellular components, for initiating and maintaining self-assembly and growth into biologically, mechanically and electronically interactive functional multi-component systems. A functional neuromuscular junction model composed of human stem cell derived motoneurons and muscle has been used to produce dose response curves for synaptic cleft toxins. Cardiac modules have been developed that allow independent evaluation of electrical conduction and force generation in cardiac muscle for mechanistic studies for both human iPSC and embryonic stem cells. These have also been combined with liver systems in the same platform to include metabolic effects that have been demonstrated with 4 different drug/metabolic pairs. Recently a 4-organ system with recirculating medium was demonstrated for 28 days and exhibited toxicity with 5 drugs that reproduced in vivo results. Detailed results with the above system will be presented as well as results from collaboration with industry partners. There is currently a focus at the NIH, FDA and EMA to understand how one could validate these systems such that qualification could be granted for their use to augment and possibly replace animal studies. This talk will also give results of six workshops held at NIH as a collaboration between the American Institute for Medical and Biological Engineering (AIMBE) and NIH to explore what is needed for validation and qualification of these new systems.
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