Pilot study investigating the use of human stem cell derived neurons in toxicity testing

Toxic chemicals can have a severe to fatal effect on the development of the brain of the human embryo; these chemicals are called developmental neurotoxins. The developing human nervous system is susceptible to many toxicants, and chemical exposure during development may cause lasting neurological deficits. As such it is necessary to test potential developmental neurotoxins to determine the safe dose of these chemicals and ensure that they are only used within safe limits. The currently accepted method of testing potential developmental neurotoxins is using animals such as mice and rats, with 34,515 animals being sacrificed for this purpose in 2005 alone. The aim of this Pilot Study is to develop a method that will greatly reduce the number of animals used in testing developmental neurotoxins by using human stem cells that we grow in the laboratory. Stem cells have the ability to produce specialised cells for various tissues in the body. The type of stem cells that we will use, develop into the type of cells that make up the human brain. The development of these stem cells into brain cells is particularly sensitive to the effects of neurotoxins. We therefore aim to develop a model where we can accurately and rapidly measure how toxic chemicals are by the degree to which they inhibit the stem cells from being able to develop into working neurones and astrocytes.

This Pilot Study seeks to develop further our in vitro model of neurotoxicity using a recently developed immortalised human embryonic stem cell line to create a rapid and high throughput in vitro biological assay that surpasses the inherent limitations of the currently accepted in vivo animal based assays. Animal use is significant for investigations into the nervous system. Indeed in 2009 procedures investigating the central nervous system accounted for the second largest number of animals used with 397,000 (11%) procedures carried out where mice, rats and fish were the most common species used (99% of this type of procedure). The long term aim of this project is to therefore replace/reduce the current in vivo methods of screening potential developmental/post-developmental neurotoxicants, thus significantly reducing the sacrifice of these animals for this purpose annually. In addition, this model will also greatly aid in the development of our other ongoing projects elucidating mechanisms of disease such as Alzheimer?s development which are heavily reliant upon the use of transgenic animals. This has the potential to significantly reduce further the use of animals in brain research.