Each year, there are 20 million broken hearts across the world. Our hearts can fail because they are getting old; because of the stresses and strains placed on our heart by the drugs we take to treat illness such as cancer; or simply because of our genetic make-up.
Imagine a world where a broken heart could be mended — not by Cupid’s arrow — but with a drug with no side effects or by an injection of new heart cells to replace the cells that have been lost or damaged. These treatments might be years or decades away but that’s what a team of scientists at The University of Nottingham is working towards.
Leading them is Chris Denning, Professor of Stem Cell Biology in the Centre for Biomolecular Sciences. He said: “We turn skin cells into stem cells and turn these stem cells into beating heart cells. For me the ultimate goal would be to develop a new drug to help peoples’ hearts. If I could achieve that in my career then I would be a happy person.”
Much of Professor Denning’s work is based on a discovery made by a team of Japanese scientists in 2006. The Japanese team discovered the four genetic factors needed to convert skin into stem cells. Their work, which revolutionised stem cell research, was recognised in 2012 with the Nobel Prize for Medicine. The technique is now being used by the Nottingham team to interrogate how heart cells work.
What happens when a heart is broken?
When someone has a major heart attack they lose between one and five billion heart cells — that is five to 20 per cent of the total number of cells in the heart. When cells die it compromises the whole structure of the heart. Scarring develops which stops it from functioning properly.
As a result lifestyle is significantly compromised and life expectancy can be as little as five years. Apart from a heart transplant there is little that can be done.
Mending a broken heart in the future
Professor Denning wants to find a way of replacing lost and damaged heart cells by ‘injecting’ new cells directly into the heart. But the challenges are huge. These new cells would be entering a toxic and hostile environment — a toxic mixture of chemicals released from the dying heart attack cells and immune cells — so 99 per cent of the transplanted cells do not survive. And if they did survive they would have a major job on their hands to keep the heart functioning properly.
Professor Denning said: “An alternative is to use precursor cells that can adapt more readily to an environment like this, which is more like war zone. This is because the precursor cells are less mature and can proliferate to make more precursor cells. They can also convert into beating heart cells and blood vessels, which means they can be used to replace the lost heart tissue.
Another challenge for cell transplantation is that the heart is a very dense muscle. This means injected cells might trickle back out of the injection site and be lost. To address this, one possibility is to design a kind of patch developed from biomaterial that can be positioned over the damaged area of the heart. We will have to look at this in a number of different ways. But whatever we develop the cells would need to fully integrate with heart function.”
In parallel research, Professor Denning’s team are trying to address the problem of people having unexpected adverse heart reactions to the medication they take for anything ranging from cancer to colds. Using complex genetic engineering he wants to recreate heart cells with the same genetic make-up as people who are likely to have an adverse reaction to these drugs.
Professor Denning said: “A minority of heart patients will experience an adverse reaction to drugs that are currently on the market. If we had a drug safety platform to test the genetic make-up of heart cells we could pin point which drugs would be safe for an individual patient to take. This would improve drug safety and significantly reduce the possible side effects, whilst simultaneously reducing the amount of animal research needed for drug development.”
Much of Professor Denning’s work is carried out in collaboration with Imperial College London and funded by The British Heart Foundation, Heart Research UK, NC3Rs, Medical Research Council, the Engineering and Physical Sciences Research Council and the Biotechnology and Biological Sciences Research Council.
He said: “If solving these challenges was simple it would have already been done, but it isn’t. We would not want to give heart patients any false hope. However, it is hoped that we can develop a drug testing platform in the next five years. Cell transplants will take much longer than that — possibly a decade or two.”
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Notes to editors: The University of Nottinghamhas 43,000 students and is ‘the nearest Britain has to a truly global university, with campuses in China and Malaysia modelled on a headquarters that is among the most attractive in Britain’ (Times Good University Guide 2014). It is also the most popular university among graduate employers, the world’s greenest university, and winner of the Times Higher Education Award for ‘Outstanding Contribution to Sustainable Development’. It is ranked in the World's Top 75 universities by the QS World University Rankings.
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