From skin cells to new neurons

Scientists at The University of Auckland’s Centre for Brain Research have succeeded in converting human skin cells directly into immature brain cells (or neural precursor cells).

The team, assisted by funding from the Neurological Foundation of New Zealand, the Auckland Medical Research Foundation, and the Maurice and Phyllis Paykel Trust, led the world in 2012 by developing a fast and efficient means of accomplishing this without having to go through the intermediate stage of conversion to embryonic stem cells.

“This is an advance of huge significance to stem cell research on a global level,” says Principal Investigator, Associate Professor Bronwen Connor, who is head of the Neural Repair and Neurogenesis Laboratory at the University. “It has the potential to lead to a new understanding of neurodegenerative diseases such as Huntington’s, Parkinson’s and Alzheimer’s.  We are all very excited about it.”

A key advantage of this research is that it enables researchers to take skin cells from patients with genetically-linked neurological diseases and use these to create brain cells which will be affected by the disease.

“This helps in gaining understanding of the mechanisms causing the disease. It will allow us to test potential treatments on actual brain tissue”, says Associate Professor Connor. “It also takes us further towards the possibility of replacing damaged brain cells.”

While teams in top universities in the United States and other parts of the world are also investigating ways of converting skin cells to brain cells, the work of The University of Auckland team is unique.

First, it is the only group to have reprogrammed adult human skin cells. Other groups using this technique are working with cells taken from animals’ skin.

Second, the Auckland team is using just two genes for the process of reprogramming from skin cells to neural precursor cells. Other international groups are using between five and 11 genes.

One effect of her team’s methods, says Associate Professor Connor, is to speed up the process. The conversion from skin cells to embryonic stem cells and then to neural precursor cells takes four months. If the skin cells are converted directly to neural precursors, this takes one and a half months or 20 days, depending on the type of technology used. The system developed by her team is also very efficient, resulting in a high conversion rate from one cell type to another.

The direct conversion also overcomes a problem of tumour formation which can arise when embryonic stem cells are used.

Associate Professor Connor and her team have for several years been looking at the possibility of using embryonic stem cells to replace brain cells injured through accident or disease. However, as she explains, the very reason for using embryonic stem cells – which is their capacity for making any type of cell in the human body – also brings a problem that has to be overcome before cell replacement can be considered.

“When creating brain cells from embryonic stem cells you have to make sure that all of them are converted. Otherwise the ones that remain can convert to other types of cells, typically cancer cells.”

The elimination of this risk through direct conversion from skin cells to neural precursor cells therefore gives a strong boost to the prospect of cell replacement therapy in the future.

The other members of Associate Professor Connor’s team are Dr Christof Maucksch, a postdoctoral fellow at The University of Auckland, and Dr Mirrella Dottori from the University of Melbourne.

First published July 2012

Promising young brain researcher returns to NZ

Hawkes Bay-born Dr Erin Cawston has been named the 2011 Neurological Foundation Repatriation Fellow. Erin will return from her position as Research Fellow at the Mayo Clinic Arizona next month, in order to further her research into Huntington’s disease at the Centre for Brain Research.

 The Repatriation Fellowship ensures outstanding young researchers who have completed postdoctoral studies overseas can return home and continue to develop their research careers in their specialist area. Dr Cawston says “I am incredibly grateful to the Neurological Foundation for this Repatriation Fellowship allowing me to come home to New Zealand. I look forward to working with Associate Professor Michelle Glass and Professor Mike Dragunow on such an exciting project as well as being back amongst the New Zealand scientific community.” Dr Cawston begins her Fellowship at The University of Auckland in February.

 Alongside this exciting research, the Neurological Foundation has also funded a number of exciting new research projects at the CBR.

 Optimising a novel induced neural precursor-like cell line Associate Professor Bronwen Connor, Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research University of Auckland, $136,862 

 The generation of ‘embryonic-like’ stem cells from adult human skin was first demonstrated in 2007. This project will advance this capability by directly generating immature brain cells (neural precursor cells) from adult human skin. Of major significance is that this will avoid the need to generate an intermediate embryonic-like stem cell phase, providing neural precursor cells for therapeutic applications without risk of tumour formation from stem cells. This project provides a unique opportunity to establish a novel technology which is likely to have wide-reaching applications for future research in the areas of neurological disease modeling, drug development, and potentially cell replacement therapy.

 A genetic mechanism underlying late-onset Alzheimer’s disease Professor Russell Snell, School of Biological Sciences University of Auckland, $86,875

 Alzheimer’s disease is a debilitating disorder affecting up to 50 per cent of those aged over 80 years old. Despite decades of research and innumerable clinical trials, there are no treatments that prevent or reverse the progression of the disease. There is currently some evidence that patients have a small proportion of brain cells with three copies of chromosome 21 instead of the normal two, leading to an increased production of the toxic protein amyloid-beta peptide. This study aims to confirm this observation, determine the pathological consequences of these cells and look for markers that make these cells different, which may lead to new therapies.

 Immodulation of stroke with risperidone Associate Professor Bronwen Connor, Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, University of Auckland, $11,999

 Stroke is a leading cause of disability in New Zealand and the burden associated with this neurological disorder is increasing. Treatment of stroke represents a large, unmet medical need. Neuroinflammation is an important pathophysiological mechanism involved in stroke and impacts profoundly on the extent of cell loss, as well as injury progression. Neuroinflammation therefore offers an exciting therapeutic target for the treatment of stroke. It has been recently demonstrated that the anti-psychotic drug, risperidone, is effective at reducing neuroinflammation and disease progression in a model of multiple sclerosis. This project will now explore whether the anti-inflammatory properties of risperidone can reduce the progression and severity of stroke. 

 Do BMP antagonists play a role in directing the fate of adult neural progenitor cells following neural cell loss?
Shwetha George, Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, University of Auckland, $4,000

 The ability for adult neural stem cells to migrate to areas of brain damage and generate replacement brain cells may provide a unique mechanism by which to develop novel therapeutic strategies for the treatment of brain injury or neurological disease. However, the local environment appears to be critical for directing the final fate of adult stem cells in the damaged brain. This study will investigate whether brain injury alters the expression of a group of compounds known as bone morphogenic protein antagonists to promote adult neural stem cells to form glial rather than neuronal cells. The results of this study will enhance our knowledge as to how stem cells respond to brain cell loss and may assist in the development of novel therapeutic strategies for the treatment of brain injury or disease.

CBR Calendar 2012 winner

Thank you for voting – the winning image from the CBR Calendar has been chosen!

Associate Professor Bronwen Connor’s lab team will receive $500 towards communicating their exciting stem cell research at a scientific conference. The winning image was: July: Making Friends by Dr Renee Gordon.

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Displaying the breadth of research underway at the CBR, the calendar showcases the wonders of the brain. You can receive a copy of the calendar with a $10 contribution towards brain research at the CBR. With every copy you order, your contribution will help our researchers working together to improve lives.

You can view the beautiful images in the calendar here.

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