Harnessing stem cells to model lung disease
The unique ability of stem cells to transform into any type of cell can help us find out what happens in the early stages of lung disease.
Medical research relies upon models to explore new ideas and enhance our understanding of how disease works. From computer based models which can help predict how and where disease will spread to the use of fruit flies to show how our genes work, models are the essential tools every scientist needs to understand our world.
However, it’s the model’s greatest advantage that is also its biggest flaw. Models can simplify complex biological interactions to help us study disease, but may miss out crucial factors which could affect how we understand disease. When using a model to find out if a particular drug might be effective, for example, we want the model to be able to accurately replicate how the drug will interact with body tissues in humans.
Idiopathic pulmonary fibrosis (IPF) is just one of many lung diseases where better models are needed. The scarring of the lung which occurs in people with IPF involves a complex biological process in the space between two distinct tissues (the air sac of the lung and the blood vessel). Because many people present with the disease at a late stage, when scar tissue has already started to build up in the lung, understanding what actually causes the scarring process to begin is difficult without resorting to a model.
Currently, scientists can conduct experiments in lung scarring using mice. The bleomycin mouse model uses an antibiotic which, when fed to the mice, replicates the scarring process in the lung over several weeks. The scarred lung tissue can then be extracted from the mice to find out which factors speed up or slow down the scarring.
The big advantage of the bleomycin mouse model is that you can activate fibrosis at any time. Being able to switch on fibrosis allows scientists to test the effectiveness of treatments at different points in the scarring process. Recent experiments using this model have identified that lung scarring can be reversed, which is a major step forward in finding new treatments.
But one crucial thing that the bleomycin model can’t do is show us what causes IPF in humans. The model is only an imperfect approximation of the effects of the disease in humans; the scarring that occurs in the lungs of people with IPF occurs over many years, not weeks. We need a model which can help scientists replicate the human version of IPF in the lab and use that model to test drugs and other potential treatments. With advances in cell culturing, we are now in a position to use human stem cells to beat this disease.
Stem cells are special cells with unlimited potential. They have the ability to become any type of cell that you need, whether that is a retina cell to help you see colour or a muscle cell to help you lift weights. The applications of stem cells in medicine are extensive and scientists are already taking advantage of this technology to tackle incurable diseases and repair broken tissues.
Thanks to new funding from the British Lung Foundation and the Masonic Charitable Foundation, a crack team of scientists will build a new model of human IPF using stem cells. Using Nobel Prize-winning technology, they can extract cells from adult patients with IPF, turn them into stem cells and then grow them into lung cells in the lab. Dr Nick Hannan, Assistant Professor of Translational Stem Cell Biology at the University of Nottingham, explains:
“Although we have learned a lot about IPF from animal models, these can only take us so far in our understanding of the factors which cause lung scarring. We need a better way to observe how scarring develops and spreads within the lung.
“Thanks to some major advances in stem cell research, we can now take almost any cell in the human body, completely rewrite its genetic code and turn it into a stem cell.
“The possibilities that this offers are endless. Being able to grow lung tissue in the lab, which perfectly matches all the characteristics of the disease, is an exciting prospect which will vastly improve our ability to find new treatments for IPF.
“Stem cell technology is revolutionising how we look at disease. IPF is a complex disease which is poorly understood, but this could change all that.”
The funding provided by the Masonic Charitable Foundation and British Lung Foundation has enabled the group to recruit a PhD student, Liam Reed, to build the stem cell model and to put it to the test against some potential treatments from IPF.
“I’ve always had a keen interest in understanding how diseases develop and stem cells offer the most accurate way to study. It’s very important to me that this project will deliver real-life benefits for the many thousands of people living with IPF in the UK right now.
“I’m very conscious of the lack of a cure for IPF and I am hoping that my project will be able to answer some of the key questions that remain around how this disease affects people.”
