Research and Innovation 2016

Using iPSC-derived neural stem cells as a CNS model to study neuronal behaviour in development and neurodegeneration

Induced pluripotent stem cell (iPSC)-derived neural cells provide a powerful tool that can be used to model neuronal behaviour and disease pathology. The increased use of these cells in drug discovery promises to help accelerate current drug screening processes and reduce the use of in vivo models used at the earliest stages of testing. Importantly, the production of specific populations, such as cortical and dopaminergic neurons, has allowed researchers to investigate the activity of neural networks from particular regions of the brain. We developed a number of endpoint assays using human iPSC-derived neural stem cells to determine the functionality of these cells and their response to toxins or disease-relevant biomarkers in both Alzheimer’s disease and epilepsy. We have also manipulated the cells using Lentivirus and have demonstrated long-term expression of over 9 months. The methods developed offer a platform to facilitate our understanding of normal physiological functions and the causes of central nervous system (CNS) pathology. 

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Modelling Alzheimer's Disease Using Stem Cells

Dr Eric Hill, Aston University, presented his research on brain hypometabolism in Alzheimer's disease progression during Research & Innovation 2016.

Currently, the majority of studies on Alzheimer's disease have used transgenic animal models or imaging studies of the human brain. It is difficult to validate these findings using human tissue. Whilst animal models have been central to our understanding of human physiology, human stem cell-based models may help us to further our understanding of human physiology and tackle devastating diseases such as Alzheimer's disease.

Dr Hill covers the following in this presentation:

  • Brain hypometabolism is a major feature of Alzheimer's disease, appearing decades before cognitive decline and pathological lesions.
  • Human stem cell-derived neuron and astrocyte cultures treated with oligomers of amyloid beta display a clear hypometabolism, particularly with regards to utilisation of substrates such as glucose, pyruvate, lactate and glutamate.
  • As many neuronal functions, such as memory formation and protection from oxidative stress require energy formed from oxidative phosphorylation, these cells are at high risk of hypometabolism.
  • Further research using models derived from iPSCs may elucidate the mechanisms associated with amyloid beta-induced hypometabolism and therefore expedite the discovery of novel biomarkers and mechanisms associated with disease progression.

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