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Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses

Neural stem cells: Image credit: Yichen Shi (Livesey Lab)


Cambridge scientists have, for the first time, created cerebral cortex cells – those that make up the brain’s grey matter – from a small sample of human skin. The researchers’ findings, which were funded by Alzheimer’s Research UK and the Wellcome Trust, were published in Nature Neuroscience.

Diseases of the cerebral cortex range from developmental conditions, such as epilepsy and autism, to neurodegenerative conditions such as Alzheimer’s disease. These findings will enable scientists to study how the human cerebral cortex develops, how it ‘wires up’ and how that can go wrong (a common problem leading to learning disabilities).

It will also allow them to recreate brain diseases, such as Alzheimer’s disease, in the lab. This will give them a previously impossible insight, allowing them to both watch the diseases develop in real time and also develop and test new drugs to stop the diseases progressing.

Cambridge Neuroscientist Dr Rick Livesey of the Gurdon Institute and Department of Biochemistry, principal investigator of the research, said: This approach gives us the ability to study human brain development and disease in ways that were unimaginable even five years ago.”

For their research, the scientists took skin biopsies from patients and then reprogrammed the cells from the skin samples back into stem cells. These stem cells as well as human embryonic stem cells were then used to generate cerebral cortex cells.

One aim of human cortical development and disease modeling is the generation of models that approximate closely with the in vivo cortex, in terms of the specificity of circuits formed and the laminar organization of the different projection neuron types. This will be particularly important for diseases of cortical synaptic function, including epilepsy, schizophrenia and cognitive impairment in dementia.

Dr Livesey added: We are using this system to recreate Alzheimer’s disease in the lab. Alzheimer’s disease is the commonest form of dementia in the world, and dementia currently affects over 800,000 people in the UK. It’s a disease that primarily affects the type of nerve cell we’ve made in the lab, so we’ve the perfect tool to create a full, human model of the disease in the lab.”

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said: “We are really pleased to have contributed funding for this work and the results are a positive step forward. Turning stem cells into networks of fully functional nerve cells in the lab holds great promise for unravelling complex brain diseases such as Alzheimer’s.

“Dementia is the greatest medical challenge of our time – we urgently need to understand more about the condition and how to stop it. We hope these findings can move us closer towards this goal.”

Article adapted from University of Cambridge Research News

Read article in The Telegraph about this research.

Posted on 07/02/2012

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