Abstract

Evaluation of Human Stem Cell-derived Neurons for Neuropsychiatric Drug Discovery and Safety Testing

Robert Halliwell, Professor in the School of Pharmacy and the School of Dentistry, University of The Pacific

Studies in neuropharmacology and neurotoxicology have relied extensively on animal models that are inefficient, costly and of poor predictive validity; there are also ethical concerns about using large numbers of animals in biomedical research. Developments in stem cell science have provided new opportunities to generate human neurons from stem cells but characterization of these cells is still at an early stage.

Our lab is investigating several sources of adult (somatic) stem, induced pluripotent stem (iPS) and embryonic stem (ES) cells to differentiate into functional human neurons. We are using patch-clamp electrophysiology, immunocytochemistry and flow cytometry to determine the neuropharmacological and neurophysiological properties of neurons derived from iPS and somatic stem cells. In addition, we are addressing the potential value of these human stem cells in vitro to predict developmental neurotoxicity that can occur in vivo through exposure to environmental agents and therapeutic medicines, including anticonvulsant drugs.

Our results will illustrate the value of stem cell-derived neurons in the discovery and development of new neuropsychiatric medicines and in the evaluation of their safety.