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 2008-2009

Characterization and evaluation of human stem cell derived neurons for developmental neurotoxicity studies

Dr RF Halliwell & Dr L Coyne
University of the Pacific

Human stem cell-derived neurons (hSCNs) may provide simple and powerful in vitro models of nervous system development but there is minimal data on their functional properties and even less establishing their validity and reliability for neurotoxicological studies.

With pilot funding from Johns Hopkins CAAT in 2007, we obtained data showing that hSCNs develop several of the molecular and electrical properties of mature human neurons and we have established that they are exquisitely sensitive to the prototype neurotoxin, methylmercury. We also observed that the effects of mercury are highly dependent on the stage of cell differentiation and, notably, that hSCNs apparently unharmed by short-term exposure to low levels of mercury, display impaired electrical properties 7-14 days later, supporting the notion of silent neurotoxicity.

The aims of this study are now to explore the sensitivity of human stem cell derived neurons to a broader range of putative neurotoxins, including ethanol and the anticonvulsants, phenobarbitone and valproic acid using both cellular and electrophysiological measures and to begin investigating the underling mechanisms for neurotoxicity.

These experiments will provide new data on the validity of human stem cell-derived neurons as simple, ethically acceptable and reliable models for neurotoxicological studies. Data generated in this study provides strong support for a reduction in the need for laboratory animals.