Abstract

The Challenge in Building Phenotype Body-on-a-Chip Models for Toxicological and Efficacy Evaluations in Drug Discovery as well as Precision Medicine

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, precision medicine has been a topic that has received much attention recently. Key characteristic needed for these systems are the ability for organ-to-organ communication in a serum-free recirculating medium and incorporation of induced pluripotent stem cells that allow for understanding genetic variation as well as to construct systems utilizing stem cells from diseased patients and also from individuals. Additional characteristics that have been discussed are functional readouts that would enable non-invasive monitoring of organ health and viability for chronic studies that now are only possible in animals or humans at this time. In addition, in order to achieve wide spread adoption of these technologies they should also be low cost, easy to use and reconfigurable to allow flexibility for platforms to be examined with small variation. Our group, in collaboration with Dr. Michael Shuler from Cornell University, has been constructing these systems with up to 6 organs and have demonstrated long-term (>28 days) evaluation of drugs and compounds, that have shown similar response to results seen from clinical data or reports in the literature. We have accomplished the construction of these systems utilizing mostly 2D systems in serum-free medium with functional readouts that employs a pumpless platform that enables ease of use of these assays. Our group’s ability to control the interface between the biological and non-biological components in these systems has enabled the straightforward integration of multiple cell types in the same platform. Results with the functional multi-organ systems will be presented as well as results of five workshops held at NIH to explore what is needed for validation and qualification of these systems by the FDA and EMA.