Mending little hearts
Mesenchymal cell plasters offer hope for children born with congenital heart disease
Professor Caputo and members of his team explain the science behind the tissue patches.
Congenital heart defects (CHDs) are amongst the most common birth defects, affecting approximately 13 babies a day in the UK. These defects develop in the womb, ranging from mild to severe, and lead to structural abnormalities that can impair the heart's ability to pump blood effectively. Repeated surgeries are often a necessary but traumatic part of life for children with these defects, which can lead to a lifetime of complications and limitations.
However, a ground-breaking new technology developed by Professor Massimo Caputo and his team at the University of Bristol offers hope for these young patients. Mesenchymal cell heart plasters, also known as heart patches, have the potential to revolutionize the treatment of CHDs by providing a regenerative solution that adapts and grows with the child's heart.
Harnessing the power of mesenchymal cells
Mesenchymal cells are a type of adult stem cell found in various tissues, including bone marrow, fat, and umbilical cord blood. These cells act as a sort of blank canvas, capable of differentiating into different cell types and promoting tissue repair.
The technology developed by the team harnesses the capabilities of mesenchymal cells to create patches or ‘plasters’ that can be seamlessly integrated into the damaged heart tissue. The patches or valves are created using a biocompatible scaffold in a shape that is unique to the anatomy of each patient and their particular defect. Mesenchymal cells are then seeded onto the scaffold, matured in vitro and implanted into the patient. This boosts the repair of heart tissue, and reduces the risk of rejection by the body.
Benefits of mesenchymal cells
- Self-renewal: replicate and maintain their stem cell characteristics, ensuring a continuous supply of cells for repair.
- Low immunogenicity: generate low immune response, meaning they are less likely to be rejected by the patient's immune system.
- Paracrine signalling: by communicating with nearby cells, MSCs can release a diverse array of growth factors and cytokines that promote tissue repair, angiogenesis (new blood vessel formation), and anti-inflammatory effects.
Eliminating the need for repeat surgeries
Traditional surgical techniques for CHDs often involve replacing damaged heart tissue with synthetic patches or grafts. While these procedures can provide temporary relief, and there have been some improvements over the years, as artificial material they do not grow with the child's heart, and can result in inflammation and calcification around the plaster and ultimately fail.
‘The main limitation of the technology currently used in clinics is the fact that it doesn’t grow with the patient, meaning the patient has to go through repeat surgeries. These numerous surgeries really affect the quality of life of the patient.’
There are around 200 repeat operations for people living with CHD in the UK every year, necessary to repair or replace the artificial technologies currently in use, costing the NHS around £30,000 for each surgery. Open-heart surgery can be hugely traumatic to both the child and family, resulting in long hospital stays and disruption to childhood. Risks of complications increase with each surgery, including hypertension, endocarditis, kidney conditions, respiratory complications and the difficulty of working with scarred tissue.
For years families have come to us asking why their child needs to have heart surgery time and time again. Although each operation can be lifesaving, the experience can put an unbelievable amount of stress on the child and their parents. We believe that our mesenchymal cell patches will be the answer to solve these problems.
A pathway to clinical application
Professor Caputo's research has demonstrated the efficacy of mesenchymal cell heart patches in preclinical studies, showing significant improvements in heart function and reduced need for surgeries. The team are now seeking validation to take the technology to clinical trials in patients. Initially this will be in patients with born with a condition called Tetralogy of Fallot, where there is a hole in the wall between the two lower chambers (ventricles) of the heart, with a narrowing of the pulmonary valve and main pulmonary artery. The team will begin an ethics application through the Medicines and Healthcare products Regulatory Agency (MHRA) next year, and hope to start a safety study by 2026.
As well as a huge impact on the lives of children with CHD, the potential use of the technology across cardiovascular surgery is immense. Professor Caputo’s team believe that the next 10 years will see major developments in the development of tissue engineering technology for personalised treatment of rare diseases
“Our ultimate vision in the next decade is to create a paradigm shift in the way doctors treat congenital heart disease, by developing personalised stem cell and genetically-engineered treatments for the most complex of heart defects.”
Professor Massimo Caputo
A unique research environment
Professor Caputo’s team undertake their work as part of the Bristol Heart Institute, a specialist research institute at the University of Bristol. The BHI is a world-leading centre for translational cardiovascular research and the leading academic cardiac surgery centre in the UK, working closely with the NHS Clinical Services team, where Professor Caputo is a Consultant in Cardiothoracic Surgery.
'The University of Bristol offers a unique environment basic scientists and clinicians like me to join forces in research’
Born with Truncus Arteriosis, Calum (centre right) received lifesaving open heart surgery from Professor Caputo when he was just ten days old. Since then, Calum has had a further four major heart surgeries – all performed by Professor Caputo and his team. Now 17, Calum and his family wanted to say thank-you to ‘their hero’. The family say thanks to Professor Caputo and his incredible team Calum has been able to achieve dreams that other boys take for granted like playing football.
Born with Truncus Arteriosis, Calum (centre right) received lifesaving open heart surgery from Professor Caputo when he was just ten days old. Since then, Calum has had a further four major heart surgeries – all performed by Professor Caputo and his team. Now 17, Calum and his family wanted to say thank-you to ‘their hero’. The family say thanks to Professor Caputo and his incredible team Calum has been able to achieve dreams that other boys take for granted like playing football.
‘It was a great honour to receive the BHF heart hero award. I would really like to thank everybody who believed in and supported this project on behalf of all these kids and families.’
A Heart Hero
Professor Caputo’s work is generously supported by the British Heart Foundation, who this year awarded £750,000 with the aim to get the patches ready for testing in patient in the next two years. His work was also recognised as one of three nominations in their ‘Research Story of the Year’ awards. The awards are ‘a chance to recognise the awe-inspiring people who have gone above and beyond to make a difference to those with heart and circulatory disease.’
On the 6 December at an awards ceremony held in London, Professor Caputo’s had won the award, taking 56% of the public vote.
Professor James Leiper, Associate Medical Director at the British Heart Foundation, said:
"We're thrilled to have awarded Research Story of the Year to Professor Caputo. Heart surgeries are a huge ordeal for children and their families, and Professor Caputo’s development of a revolutionary ‘heart plaster’ could in future help children with congenital heart disease avoid having multiple surgeries. This award is a testament to Professor Caputo’s pioneering approach to mending hearts, and we’d like to congratulate him and his team on their achievement.”
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