The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 2007-2008

Neural Stem Cells: A Powerful Alternative Model to Cultured Animal Neurons for Developmental Neurotoxicological Studies

RF Halliwell, PhD
University of the Pacific

Neural Stem Cells may revolutionize the treatment of human disease and the discovery of new drugs. They may also prove powerful in vitro models for the investigation of the toxicological effects of drugs and environmental agents on the nervous system. Stem cells might ultimately replace animal–derived tissues for scientific experiments.

Stem cells are self-renewing with the capability of forming any cell type, tissue or organ in the body. Stem cell-derived neurons (SCNs) can now be grown in vitro allowing their properties to be studied but currently there is little data establishing their functional properties. Indeed there is evidence that SCNs express some nerve cell protein markers but may not display their electrical properties. The goals of this project are to characterize the physiological and pharmacological properties of neurons derived from the embryonal carcinoma-derived stem cells, TERA2.cl.SP12 and to establish their validity for the investigation of neurotoxins. This study will utilize electrophysiological and some molecular biological methods. The main aims of this project are to determine (1) the properties and electrical activity of SCNs maintained in cell culture; (2) the identity of the receptors (through which drugs and toxins can act) that are expressed in these neurons and (3) the sensitivity of SCNs to selected neurotoxins. These experiments will provide new data on the functional properties of neurons derived from stem cells and their value as simple in vitro models for the investigation of the neurotoxicological actions of xenobiotics and the biological mechanisms that underlie their actions.