Neurons from stem cells for neuropharmacology and neurotoxicology studies
John C. Livesey: 0000-0001-9010-5970
Conference Title/Conference Publication
British Neuroscience Association 2013: Festival of Neuroscience
Barbican Centre, London, UK
April 7-10, 2013
Date of Presentation
Since the isolation and culture in vitro of human pluripotent embryonic stem cells in 1998, a number of alternative sources of human stem cells have been identified, including neural stem cells in the central nervous system. Enormous excitement surrounds these unique cells because of their potential value in regenerative medicine and in drug discovery and development. Few studies to date, however, have characterized the functional properties of neurons derived from human stem cells or addressed their value in drug safety testing. Over the past several years, this lab has begun to investigate the neurophysiological and neuropharmacological properties of neurons derived from a variety of human stem cell sources including fetal neural stem cells, embryonal carcinoma stem cells and dental pulp stem cells. We are also investigating their validity for assessing the risk of drug-induced developmental neurotoxicity in vitro.
Human stem cells are cultured in vitro and differentiated using a variety of media and growth factors. Neural and glial cells are differentiated and used in experiments between 10 and 120 days in vitro. Characterization of cells is conducted using cell morphology, immunocytochemistry, flow cytometry and patch-clamp electrophysiology.
This presentation will describe our results showing that human stem cells from different sources can develop the morphological features of neurons and glia, display immunocytochemical markers and express a complex array of functional voltage- and ligand-gated ion channels; the advantages and challenges of using different types of human stem cells to derive neurons will be also be considered. Finally, data will be presented showing the sensitivity of human stem cells and their neural phenotypes to a range of clinically important psychotropic agents.
Overall, our data support the high potential value of human stem cells for academic neuropharmacology studies and as new tools in drug discovery and drug safety assessment. However, there is still a considerable volume of research required to optimize the differentiation of stem cells into specific neural phenotypes and to fully characterize the array of receptor families, ion channels and their subtypes these cells express in vitro.
Halliwell, Robert F.; Coyne, Leanne; Cao, William S.; and Livesey, John C., "Neurons from stem cells for neuropharmacology and neurotoxicology studies" (2013). School of Pharmacy Faculty Presentations. 348.