Using human embryonic stem (ES) cells as a cell source to model disease is an exciting approach to advancing our understanding of the causes of a given disease. Studying a "disease in a dish" is now possible because we now can create a sufficient quantity of specific cells needed for large-scale automated screens that can help identify factors involved in disease etiology, potential drug targets, and compounds that might be pursued through drug discovery pathways. In a recent example of this approach, HSCI faculty member Kevin Eggan and colleagues created large numbers of different neuronal subtypes from ES cells and used them to explore the disease mechanisms involved in the neurodegenerative disease ALS (Lou Gehrig's disease). Eggan and colleagues used ES derived motor neurons and interneurons cultured with glial cells (cells that provide support and nutrition for neurons) containing a mutation associated with ALS. They found that while the motor neurons were sensitive to the effects of the glial cell mutation, the ES derived interneurons were not, demonstrating selective sensitivity among neuron types. The study then goes on to use the ES derived motor neurons to identify candidates whose differential gene expression in the glial cells may be responsible for the toxic effect in the motor neurons, and identified Prostaglandin D2 as having a significant effect on motor neurons. This study represents a dramatic proof of concept for the use of human ES derived cell types as a way to understand disease mechanisms and identify ways to treat the disease. This approach will be further tested in ALS and extended to other disease models.

Di Giorgio, F.P., Boulting, G.L., Bobrowicz, S., Eggan, K.C. (2008). Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell Stem Cell 3, 637-48.