Chapter 14

Pluripotent Stem Cells for (Neurodegenerative) Disease Modelling

Greg T. Sutherland and Kuldip S. Sidhu

Abstract

The prevalence of late-onset neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease is increasing alarmingly worldwide but their causes remain largely unknown. In order to study the pathogenesis of these diseases researchers use a variety of models from cell culture through to full organisms. As the complexity of the model system increases so does the potential variables that can confound experimental results and interpretation. Transgenic animal models are the workhorses of disease research but they have been purposefully intra-bred to remove their genetic variability, a major factor in human neurodegenerative disease. Prior to stem cell advances, researchers could obtain differentiated cell types such as fibroblasts from patients and these had reasonable longevity in the laboratory. However it was questionable how much fibroblasts could tell us about the relative susceptibilities of cells in the human brain. Embryonic stem cell lines provided the flexibility to produce all the different cell types of the body including neurons but they were derived from a limited number of individuals. It was the discovery of induced pluripotency by Yamanaka and colleagues that allowed neurons to be produced from a number of patients and unaffected controls. Now individual genetic variability could be incorporated into our experimental paradigms. Looking forward, induced pluripotent stem cells (iPSC) can be perturbed with putative toxins to re-create the natural history of a disease. This in vitro phenotype can then be used for the high throughput screening of therapeutic agents. The latter is akin to a “cure in a dish”.

Total Pages: 205-219 (15)

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