Stem Cell Derived Human-on-a-chip Systems for Use in Efficacy and Toxicological Investigations in Pre-clinical Drug Discovery

One of the primary limitations in drug discovery and toxicology research is the lack of good model systems between the single cell level and animal or human systems. This is especially true for neurodegenerative diseases such as ALS, Alzheimer’s, and spinal cord injury. In addition, with the banning of animals for toxicology testing in many industries body-on-a-chip systems to replace animals with human mimics is essential for product development and safety testing. Our research focus is on the establishment of functional in vitro systems to address this deficit where we seek to create organs and subsystems to model motor control, muscle function, myelination and cognitive function, as well as cardiac subsystems. The idea is to integrate microsystems fabrication technology 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. Our advances in culturing adult rat, mouse and human mammalian spinal cord, hippocampal neurons, muscle and cardiac cells in a defined serum-free medium, suggest outstanding potential for answering questions related to maturation, aging, neurodegeneration and injury. We are using this ability to manipulate the biological systems and integrate it with silicon-based systems to create cell-based sensors for high content drug discovery. We are also using what we learn for a more fundamental understanding of cellular development, protein adsorption and neuronal regeneration. Examples will be given of some of the more advanced body-on-a-chip systems being developed as well as the results of five workshops held at NIH to explore what is needed for validation and qualification of these systems.

Biography: Dr. James J. Hickman is the Founding Director of the NanoScience Technology Center and a Professor of Nanoscience Technology, Chemistry, Biomolecular Science, Material Science and Electrical Engineering at the University of Central Florida. Previously, he held the position of the Hunter Endowed Chair in the Bioengineering Department at Clemson University. Dr. Hickman has a Ph.D. from the Massachusetts Institute of Technology in Chemistry. For the past twenty-five years, he has been studying the interaction of biological species with modified surfaces, first in industry and in the latter years in academia. While in industry he established one of the first bioelectronics labs in the country that focused on cell-based sensors and their integration with electronic devices and MEMS devices. He is interested in creating hybrid systems for biosensor and biological computation applications and the creation of functional in vitro systems for human body-on-a-chip applications. He has worked at NSF and DARPA in the area of biological computation. He is also the founder and current Chief Scientist of a biotechnology company, Hesperos, that is focusing on cell-based systems for drug discovery and toxicity. He has 134 publications and 20 book chapters, in addition to 21 issued patents out of 44 total patent applications. He is a Fellow of both the American Institute of Medical and Biomedical Engineers (AIMBE) (2004) and the American Vacuum Society (AVS) (2007). He was a Board Member for AIMBE from 2009-2013 and Co-Chaired 6 AIMBE/NIH Workshops on “Validation and Qualification of New In Vitro Tools and Models for The Pre-clinical Drug Discovery Process” held at the NIH Campus, Bethesda, MD (2012 – 2017). He was also a Charter Member, NIH Bioengineering of Neuroscience, Vision and Low Vision Technologies (BNVT) Study Section. Dr. Hickman along with Dr. Michael Shuler, won the Lush Prize, in the Science Category, which Supports Animal Free Testing in 2015.