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Hole in the heart (Nonesuch autumn 2016)

© Andrew Baker

© Andrew Baker

7 November 2016

Congenital heart disease is the most common type of birth defect, with between six and 13 diagnoses for every 1,000 live births. Advances in treatment and care could mean that babies born with a ‘hole in the heart’ have just one operation which will last their whole life. Nonesuch explores how researchers at the University of Bristol are revolutionising heart surgery for young children.

Imagine going in for a prenatal checkup, expecting all to be well, but it’s not. Your baby has congenital heart disease (CHD). This means there is a small puncture between chambers in your baby’s heart, dangerously altering the flow of blood through their body. With a hole in the heart, oxygen-rich blood mixes with oxygen-poor blood that has already delivered oxygen and nutrients around the body.

Artificial grafts can be created using prosthetic materials, a treatment that has saved lives, but not without significant problems. These new valves, conduits and patches are applied through surgery soon after birth but they can’t match the growth of a baby’s heart. Parents have no choice but to put their child through an endless cycle of risky and distressing operations to replace the failed grafts and correct recurrent dysfunction – only to be back in hospital a few years later.

Cardiac imaging techniques have shown that this method of reconstruction is also associated with abnormalities, which can lead to thickening and scarring of connective tissue, and calcification. For most, the long-term outcomes remain poor, significantly affecting quality of life. But there is good news. Researchers at the University of Bristol have found a solution to these problems. The
team has conducted cutting-edge research into regenerative medicine, involving the use of stem cells to regenerate defective human heart and blood vessel tissues. Their research means that one operation could be enough to heal a congenital heart defect for life.

Pioneered at Bristol

Congenital heart disease research at Bristol has expanded substantially in recent years and it now brings together experts from many different departments across associated hospitals. The Bristol Heart Institute is recognised internationally as a centre of excellence for carrying out interdisciplinary cardiovascular research that can bridge the void between clinical and basic science. Stem cell therapy and tissue engineering promises nothing short of a revolution in medicine.

Led by Professor Massimo Caputo and Professor Paolo Madeddu, the approach that Bristol’s research team is investigating has the potential to completely transform treatment of CHD. Indeed, it could produce the ideal graft, as explained by Caputo: ‘Umbilical stem cells are multipotent, so they can be used to generate most components of cardiac tissue, making them ideal for use in the new treatments Bristol researchers have developed. By using the patient’s own stem cells, there is no danger of rejection or infection. We’ll create a structure that is durable, biocompatible, won’t provoke an adverse immune response and won’t cause blood clots.’

Bristol leads the way

The work done by Caputo’s team has provided the first ever evidence that cells can be seeded onto a matrix that is of clinical grade and ready to be implanted. They hope to build new heart valves using cells from the patient’s own body, with two procedures left to complete before they can embark on a first-in-human trial. The regenerative technique brings a crucial advantage: once implanted in the defective heart, the biological structures can grow and remodel with the heart and body. This removes the need for multiple surgeries.

‘Grafts currently used to repair complex problems within the structure of a child’s heart need to be replaced over time as the child grows,’ says Caputo. ‘One operation could last a lifetime if we engineer the heart valves to match the growth of a child’s heart, reducing the number of surgeries that a child born with congenital heart disease must go through.’

Exploring all avenues

In 60 per cent of all cases of CHD, the heart defect is not discovered until after birth, when access to the umbilical cord and its multipotent stem cells (so-called ‘master cells’ that have the potential to produce many of the cells or tissue the body needs to repair itself) are no longer available. Bristol’s research team has identified this secondary and equally urgent need and is prepared to undertake parallel studies to investigate the possibility of alternative sources of stem cells. To date, cells from the thymus (an organ of the immune system that is located in front of the heart and behind the sternum) have been identified as possible alternatives to umbilical stem cells.

From bench to bedside

What makes the Bristol team stand out is that it is one of the few research-active units focusing on congenital and paediatric heart surgery research. There are simply not many cardiovascular research centres that include as many clinicians – and particularly surgeons – as Bristol does. This also helps to make it an attractive place for researchers. With experts in translational cardiovascular medicine, stem cells, tissue engineering and cardiac surgery, Bristol also has one of the few teams with experience of conducting several randomised controlled paediatric CHD surgery trials.

Cellular and molecular biologist Dr Mohamed Ghorbel, a member of the University’s CHD research team explains: ‘Translational medicine is a rapidly growing discipline in biomedical research and aims to speed up the discovery of new diagnostic tools and treatments by using a multidisciplinary, highly collaborative, bench-to-bedside approach. It’s one of our focal points here at Bristol.’

Ghorbel attributes this approach to the team’s success, explaining how the challenge of translational research is that it necessitates multidisciplinary team work. ‘In the case of biomedical sciences, translating research from bench to bedside requires collaboration between basic scientists and clinicians,’ adds Ghorbel. ‘The strength of this approach at Bristol lies in strong research-minded clinicians keen to work very closely with strong basic scientists in research, for the ultimate benefit of the patient.’ 

Further information

Thank you
Generous support from a range of individual donors and charitable trusts has been instrumental in making this project a success, including the British Heart Foundation, Medical Research Council, The Mahoro Charitable Trust, Sir Jules Thorn Charitable Trust, Enid Linder Foundation, and the Garfield Weston Trust. If you are interested in supporting this ground-breaking research
please visit