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 1998-1999

ES-Derived Neurons and Glia: a Novel Cell Line Model for CNS Testing

David I. Gottlieb, PhD
Washington University School of Medicine, St. Louis, Missouri

Final Report

Embryonic stem (ES) cells of the mouse straddle the world of normal cells and tissue culture cell lines. In one type of culture they replicate indefinitely as undifferentiated cells and provide an infinite source. When transplanted into an early embryo, they integrate into the host and, under guidance of the normal cues of development, differentiate into all cell types of the host's body. ES cells are thus "stem cells for the whole body." Previously, Gottlieb and colleagues discovered a method of giving cultures of ES cells instructions so that they differentiate into neurons and glia. The resulting neurons have all the basic properties of normal neurons from the brain. Thus, it is possible to go from rapidly dividing stem cells all the way to mature and functional neurons entirely in a dish. Such a system should be ideal for testing chemicals for CNS toxicity. The investigator plans to test the effects of lead and alcohol on ES-derived neurons and compare the effects to those on cultured neurons from the brain. Gottlieb hypothesizes that the effects of lead and alcohol should be very similar in both systems, demonstrating that ES-derived neruons and glia are a valid alternative to cultured barin neurons. Because ES cells replicate indefinitely in culture they have the potential to greatly reduce the usage of animals in testing for neurotoxicity.