Building brain in a dish: how can stem cells help us to understand dementia?

Selina Wray is an Alzheimer’s Research UK Senior Research Fellow at UCL Institute of Neurology. Her research interests are focussed on understanding the molecular mechanisms of Alzheimer’s Disease and other forms of dementia using patient-derived stem cell models. Last year, she took part in the Pint of Science festival where she discussed technological advances such as our ability to grow human brain cells in the laboratory, and how these are accelerating our understanding of dementia and improving diagnosis and the development of potential treatments. Here, she shares what she and her colleagues have been up to in the lab. 

 

Alzheimer’s Disease (AD) and other forms of dementia represent a huge public health challenge: there are currently 850,000 people in the UK alone living with dementia, and currently no treatments are available that can slow down or halt progression of diseases such as AD. Diseases such as AD are caused by the progressive death of brain cells (neurons). Our progress towards finding effective treatments would be greatly enhanced by in vitro models (i.e. cells that can be grown in the lab) that capture key features of early stages of the disease, allowing us to understand and eventually prevent the processes leading to neuronal death.

However, this has been challenging for conditions affecting the brain, which remains largely inaccessible to us during life and can only be studied post-mortem, at the end stage of disease when the damage is already done and it is difficult to piece together a sequence of events from tissue examined at a single time point. Further, the human brain is different to that of other animals in terms of its size and complexity, so it is important that we study these diseases specifically in the human brain cells that they affect.

Our ability to study disease affecting the human brain has been revolutionized by the development of iPSC technology. Click To Tweet

Our ability to study disease affecting the human brain has been revolutionized by the development of induced pluripotent stem cell (iPSC) technology. First described in 2006, and awarded the Nobel Prize in 2012, this is our ability to take an easily accessible cell type, such as skin cells, and reset them to an unspecialized state – i.e. turn them into stem cells. Because stem cells have the potential to become any of the cell types of the human body, we can take a small bit of skin from a person with dementia who consents to participate in research, use this to generate that persons stem cells, and subsequently convert those stem cells into neurons. This means we have “brain in a dish” models where we can compare cells from people with and without dementia, to understand what causes brain cells to become dysfunctional and eventually die in disease.

Stem cell-derived neuronal rosettes.

This is what we have been doing at UCL for a number of years, collaborating closely with our clinical colleagues to ask people to participate in this project and growing cells from a wide range of people with different types of dementia. Although “brain in a dish” is a catchy turn of phrase, it is important to point out that what we grow in the lab does not really resemble the human brain in terms of size, complexity, and organization. The cell culture conditions we use limit the size of the brain cell cultures and the amount of time we can keep them alive, and we only have a very small percentage of the different cell types present in the brain within our cultures. So, it is a reductionist model, but still our only opportunity to have an unlimited supply of brain cells that we can study in the lab.

Have they told us anything about dementia? So far, results are positive. Click To Tweet

Have they told us anything about dementia? So far, results are positive. Our group and many others have shown that patient-derived neurons can show key changes that are also seen in the brain, and these can be used to study disease mechanisms or the “order of events” of what goes wrong. Further, these models can also be used for drug screening to find molecules that can put things right and may eventually make it into clinical trials. There is still a long way to go, but patient cells represent another weapon in our arsenal in the fight against dementia.

Resources

www.eurostemcell.org

www.alzheimersresearchuk.org

 


Opinions in this blog post are that of the author, and not necessarily that of Hindawi. All photos were provided by Selina Wray. The text in this blog post is by Selina Wray and is distributed under the Creative Commons Attribution License (CC-BY). Illustration by Hindawi and is also CC-BY.