Massimo Caputo, BHF Professor of Congenital Heart Surgery and Consultant in Cardiothoracic Surgery at the Bristol Heart Institute, received his award at a ceremony in London last night, Wednesday 6 December. The BHF’s Heart Hero Awards recognise people who have gone the extra mile to help those with a heart and circulatory disease. Read the full story
Author: clare.williams
Bristol researcher shortlisted for BHF Heart Hero Award for work on children’s heart plaster
Press release issued: 31 July 2023
A University of Bristol researcher who developed a new revolutionary type of ‘heart plaster’ that could improve the way surgeons treat children living with congenital heart disease has been shortlisted for the British Heart Foundation’s (BHF) Research Story of the Year, part of the charity’s annual Heart Hero Awards.
Massimo Caputo, BHF Professor of Congenital Heart Surgery in the Bristol Heart Institute at the University of Bristol, developed the first type of mesenchymal cell patch to repair abnormalities to parts of the heart that control blood flow from the heart to the lungs, and to mend holes between the two main pumping chambers of the heart.
Mesenchymal cells are a type of cell that have the ability to change into a range of cell types including muscle and cartilage. The patches have the potential to adapt and grow with the child’s heart as they get older, removing the need for repetitive heart surgeries as the heart gets bigger, and the many days at hospital recovering after each one.
The British Heart Foundation’s Heart Hero Awards recognise the awe-inspiring people who have gone the extra mile to help those with a heart and circulatory disease. This year‘s Research Story of the Year Award highlights three innovative BHF-funded research projects that have made a huge impact this year. The public can vote for their favourite on the BHF website until Sunday 20th August, and the winner will be announced at an awards ceremony on Wednesday 6th December.
Heart defects are the most common type of anomaly that develop before a baby is born, with around 13 babies diagnosed with a congenital heart condition every day in the UK. These include defects to the baby’s heart valves, the major blood vessels in and around the heart, and the development of holes in the heart.
Currently, for many of these children, surgeons can perform open-heart surgery to temporarily repair the problem, but the materials used for the patches or replacement heart valves cannot grow with the baby and degenerate with time. This means they can fail in a few months or years.
A child might therefore have to go through the same heart operation multiple times throughout its childhood, which keeps them in hospital for weeks at a time, hugely impacts their quality of life and causes a lot of stress for the family.
The mesenchymal cell plasters are designed to be sewn into the area of the child’s heart that needs repairing during surgery. The cells could then boost the repair of heart tissue without being rejected by the child’s body.
There are around 200 repeat operations for people living with congenital heart disease every year in the UK. The researchers estimate the technology could save the NHS £30,000 for every operation no longer needed, saving millions of pounds each year.
Professor Caputo aims to get these patches ready for testing in patients so clinical trials can start in the next two years, enabling more children and babies to benefit from the life-altering technology. The materials have already proven to work safely in animals.
Professor Caputo said: “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.
“My team and I are very proud to be shortlisted for the BHF’s Heart Hero Awards. It is an amazing recognition of all the work we have done to get to this point. We think that, with the BHF’s continuing support, these patches can soon be used widely to prevent the distress and dangers of repeated surgeries.“
Cast your vote for BHF Media Awards 2023 – Research Story of the Year here: bhf.org.uk/researchstoryvote
Further information
About the British Heart Foundation
It is only with donations from the public that the BHF can keep its life saving research going. Help us turn science fiction into reality. With donations from the public, the BHF funds ground-breaking research that will get us closer than ever to a world free from the fear of heart and circulatory diseases. A world where broken hearts are mended, where millions more people survive a heart attack, where the number of people dying from or disabled by a stroke is slashed in half. A world where people affected by heart and circulatory diseases get the support they need. And a world of cures and treatments we can’t even imagine today. Find out more at bhf.org.uk
How the University of Bristol’s research and teaching has helped shape the NHS and save lives
Press release issued: 5 July 2023
Today [Wednesday 5 July] we celebrate 75 years of the NHS – the first universal health care system to be established anywhere in the world.
Since it was established in 1948, the National Health Service (NHS) has become one of the nation’s most-loved institutions, playing a vital role in our lives.
We are proud to work closely with the NHS, from training the doctors, specialist surgeons and dentists of tomorrow, to research breakthroughs today.
We’re also shining a spotlight on how, by working closely with colleagues in Bristol’s two large NHS hospitals – North Bristol NHS Trust (NBT) and University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) – our research and teaching has helped to shape the NHS and improve people’s health:
Bristol had a medical school long before the current University received its Royal Charter in 1909. Founded in 1833, Bristol Medical School educated scholars from the city and beyond, including the famous cricketer W.G. Grace, who enrolled at the Medical School in 1868. In 1893, the Medical School was incorporated into what was, for a short time, University College, Bristol.
Medicine has been taught at Bristol on a continuous basis since the first Medical School. It now comprises around 1,327 students and around 900 staff, who through research and teaching improve the health of individuals and populations locally, nationally and internationally. Nearly 6,000 students have graduated in medicine over the past 30 years.
Thirty-one years ago, Professor Peter Fleming pioneered research which showed lives could be saved if babies were placed on their backs – and not their fronts – to sleep. It is estimated his research has saved the lives of more than 20,000 babies in the UK alone and has changed official advice about safer sleeping for babies the world over.
3. Cooling baby treatment one of ‘Nation’s Lifesavers‘
Marianne Thoresen, Professor of Neonatal Neuroscience, discovered that cooling babies who have suffered a lack of oxygen at birth improves their survival without brain damage in later childhood. Professor Thoresen was named by Universities UK as one of the ‘Nation’s Lifesavers’. This approach has already saved 1,500 babies from death and disability each year.
4. Largest ever pneumonia trial to be carried out
Over 22,000 participants will be recruited in the largest ever trial to investigate whether aspirin can reduce the risk of a heart attack or stroke in patients who are admitted to hospital with pneumonia. Led by Bristol, sponsored by NBT and supported by the Bristol Trials Centre, the ‘Aspirin after hospitalisation with Pneumonia to prevent cardiovascular Events randomised Controlled Trial’ (ASPECT) will invite adults over 50 who have been admitted to hospital with pneumonia to take part over the next four years.
5. New guidance on hip fracture services will improve recovery for thousands of patients
A new ‘toolkit’ for senior doctors and hospital managers, that will help make changes to their organisational arrangements and improve the quality of hip fracture care across the UK, has been launched by The Royal Osteoporosis Society (ROS) in collaboration with University researchers.
The guidance was developed after the REDUCE study, carried out by the University, found how well patients recover after a hip fracture varies enormously between NHS hospitals in England and Wales.
6. Bristol Network awarded Tessa Jowell Centre of Excellence status for brain tumour research
With 12,000 people diagnosed with a brain tumour every year in the UK, there has never been a more important time to recognise the efforts of NHS staff committed to developing and improving brain tumour treatment and care.
The Bristol Network, which includes NBT, UHBW, Gloucestershire Hospitals NHS Foundation Trust and Royal United Hospitals Bath NHS Foundation Trust, was recognised for its commitment to service development, in particular the further development of its rehabilitation pathways.
It is hoped that for the 88,000 British people currently living with a brain tumour, the Excellence status provides reassurance about the availability of excellent care and commitment to improvement in the NHS across the UK
7. Bristol childhood obesity clinic forms blueprint for national NHS pilot
The Care of Childhood Obesity (CoCo) at the Bristol Royal Hospital for Children is led by clinicians and researchers from the University, UHBW and the National Institute for Health Research Bristol Biomedical Research Centre (NIHR Bristol BRC). It treats children experiencing health complications related to severe obesity, and offers children specialist treatment tailored care packages developed with their family, which could include diet plans, mental health treatment and coaching. In 2021, 15 new specialist NHS services were created, based on the Bristol clinic.
8. Bristol’s research plays a key role in the world’s response to COVID-19
Collaborating with colleagues at UHBW and NBT, Bristol researchers carried out clinical trials to assess how well certain vaccines worked to prevent people from becoming infected with COVID-19.
Longitudinal studies, also carried out by University and NHS teams, explored the impact of lockdowns and the pandemic on mental health and antibody testing.
9. Pfizer’s Vaccine Centre of Excellence launches at the University of Bristol
In 2021, a new Pfizer Centre of Excellence for Epidemiology of Vaccine-preventable Diseases was launched at the University.
The centre conducts real-world population-based surveillance studies in hospitals and the community to identify and measure the burden of specific vaccine-preventable infectious diseases affecting adults, including the elderly, as well as children. Research will also be undertaken to support the design, development and use of next-generation vaccines.
10. How the University of Bristol supported NHS staff and volunteers during the pandemic
During the Covid pandemic, 100 rooms in the University’s student accommodation were given to NHS workers and volunteers. The University also made two of its biggest car parks available to NHS staff at UHBW, and donated personal protective equipment, such as suits, goggles, gloves and masks to the South Western Ambulance Service and NHS workers.
Almost 300 fifth year medical students joined the frontline prior to their graduation to help the NHS.
The University led the first clinical trial to increase the identification and treatment of hepatitis C virus (HCV) patients in primary care, which was found to be effective, acceptable to staff and highly-cost effective for the NHS.
Around 143,000 people in the UK have chronic HCV infection. As symptoms do not appear for several years, less than half of people infected are aware they have HCV and many more are not receiving treatment, increasing the risk of liver damage and passing the virus to others.
Looking to the future, the University of Bristol is working on dozens of research projects which could revolutionise NHS healthcare:
Red blood cells grown in a laboratory have now been transfused into another person in a world first clinical trial led by a UK team including Bristol researchers. If proved safe and effective, manufactured blood cells could in time revolutionise treatments for people with blood disorders such as sickle cell and rare blood types.
13. Mesenchymal cell plasters to stop children needing repeated heart surgeries
University researchers, funded by the British Heart Foundation (BHF), have developed ‘mesenchymal cell plasters’ to revolutionise the way surgeons treat children living with congenital heart disease, so they don’t need as many open-heart operations.
There are around 200 repeat operations for people living with congenital heart disease every year in the UK. The technology could save the NHS an estimated £30,000 for every operation no longer needed, saving millions of pounds each year.
Anti-aging gene shown to rewind heart age by 10 years
Press release issued: 23 January 2023
An anti-aging gene discovered in a population of centenarians has been shown to rewind the heart’s biological age by 10 years. The breakthrough, published in Cardiovascular Research and led by scientists at the University of Bristol and the MultiMedica Group in Italy, offers a potential target for patients with heart failure.
Associated with exceptional longevity, carriers of healthy mutant genes, like those living in blue zones of the planet, often live to 100 years or more and remain in good health. These individuals are also less prone to cardiovascular complications. Scientists funded by the British Heart Foundation believe the gene helps to keep their hearts young by protecting them against diseases linked to aging, such as heart failure.
In this new study, researchers demonstrate that one of these healthy mutant genes, previously proved particularly frequent in centenarians, can protect cells collected from patients with heart failure requiring cardiac transplantation.
The Bristol team, led by Professor Paolo Madeddu, has found that a single administration of the mutant anti-aging gene halted the decay of heart function in middle-age mice. Even more remarkably, when given to elderly mice, whose hearts exhibit the same alterations observed in elderly patients, the gene rewound the heart’s biological clock age by the human equivalent of more than ten years.
Professor Madeddu, Professor of Experimental Cardiovascular Medicine from Bristol Heart Institute at the University of Bristol and one of the study’s authors, explained: “The heart and blood vessel function is put at stake as we age. However, the rate at which these harmful changes occur is different among people. Smoking, alcohol, and sedentary life make the aging clock faster. Whereas eating well and exercising delay the heart’s aging clock.
“In addition, having good genes inherited from parents can help to stay young and healthy. Genes are sequences of letters that encode proteins. By chance, some of these letters can mutate. Most of these mutations are insignificant; in a few cases, however, the mutation can make the gene function worse or better, like for the mutant anti-aging gene we have studied here on human cells and older mice.”
The three-year study was also performed in test tube human cardiac cells in Italy. Researchers from the MultiMedica Group in Milan led by Professor Annibale Puca, administered the gene in heart cells from elderly patients with severe heart problems, including transplantation, and then compared their function with those of healthy individuals.
Monica Cattaneo, a researcher of the MultiMedica Group in Milan, Italy, and first author of the work, said: “The cells of the elderly patients, in particular those that support the construction of new blood vessels, called ‘pericytes’, were found to be less performing and more aged. By adding the longevity gene/protein to the test tube, we observed a process of cardiac rejuvenation: the cardiac cells of elderly heart failure patients have resumed functioning properly, proving to be more efficient in building new blood vessels.”
Centenarians pass their healthy genes to their offspring. The study demonstrates for the first time that a healthy gene found in centenarians could be transferred to unrelated people to protect their hearts. Other mutations might be found in the future with similar or even superior curative potential than the one investigated by this research. Professor Madeddu and Professor Annibale Puca of the MultiMedica Group believe this study may fuel a new wave of treatments inspired by the genetics of centenarians.
Professor Madeddu added: “Our findings confirm the healthy mutant gene can reverse the decline of heart performance in older people. We are now interested in determining if giving the protein instead of the gene can also work. Gene therapy is widely used to treat diseases caused by bad genes. However, a treatment based on a protein is safer and more viable than gene therapy.
“We have received funding from the Medical Research Council to test healthy gene therapy in Progeria. This genetic disease, also known as Hutchinson-Gilford syndrome, causes early aging damage to children’s hearts and blood vessels. We have also been funded by the British Heart Foundation and Diabetes UK to test the protein in older and diabetic mice, respectively.”
Annibale Puca, Head of the laboratory at the IRCCS MultiMedica and Professor at the University of Salerno, added: “Gene therapy with the healthy gene in mouse models of disease has already been shown to prevent the onset of atherosclerosis, vascular aging, and diabetic complications, and to rejuvenate the immune system.
“We have a new confirmation and enlargement of the therapeutic potential of the gene/protein. We hope to test its effectiveness soon in clinical trials on patients with heart failure.”
The study is funded by the British Heart Foundation and the Italian Ministry of Health.
Paper
‘The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy‘ by Annibale Puca et al. in Cardiovascular Research [open access]
The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy
Professor Paolo Madeddu and his team are working to delay the ageing of the heart. He tells Dr Leanne Grech how this research could allow older people to live a healthier life for longer.
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The BPIFB4 gene has been associated with exceptional longevity
Each day, your heart beats around 100,000 times, pumping about eight pints of blood around your body. By the time you are 20, the heart’s function can begin to decline as part of normal ageing. As you get older, activities like running or playing tennis become more difficult. However, some 100-year-olds, like those living in Okinawa, a cluster of islands in southern Japan, appear to have unlocked the secret to a long and healthy life, with some of them seemingly having a heart younger than their age. “It’s a combination of a good lifestyle and good genes,” explains Professor Paolo Madeddu at the University of Bristol. “And we have discovered that one of these good genes can stop ageing.”
The gene that can stop ageing Professor Madeddu and his team have discovered that a naturally occurring variant of the BPIFB4 gene, which is more common in people who live to 100 or more, could help keep the heart young. A gene variant is a permanent change in the DNA sequence that makes up a gene. The team have already learned that mice treated with this variant have healthier hearts. In fact, transferring this gene variant to old mice seemed to help relax blood vessels in mice with high blood pressure and increase the amount of blood delivered to the muscles. In humans, ageing can affect many parts of the body, including weakening the heart and circulatory system. For example, heart failure, a serious and sometimes disabling condition for which there is no cure other than a heart transplant. Symptoms include breathlessness and feeling abnormally tired. Heart failure can occur at any age, but it is more common in older people, and in people who have had a heart attack and who have cardiomyopathy or high blood pressure.
Scientists are now beginning to understand how some natural variations in our genes might protect against heart diseases linked to ageing, such as heart failure. In this study, Professor Madeddu and his team in Bristol have been funded by the BHF with more than £172k to further investigate the role of the BPIFB4 gene variant. The BPIFB4 gene has been associated with exceptional longevity, helping protect against atherosclerosis (build-up of fatty material inside your arteries) and high blood pressure. The team now want to know if this gene variant can be given as a tablet and if it can reduce chronic inflammation (a damaging set of processes often seen in ageing hearts). Most genes contain the information needed to make functional molecules called proteins. Giving the corresponding protein as a pill instead of the gene variant could be an easier way to get the same result. Professor Madeddu and his team will test this idea in mice. If it succeeds, they hope to go on to a clinical trial in humans. “The study will provide proof of concept that our solution is valid. More studies are needed to show it is also safe – the fact that it is a human protein and not a [new] drug is encouraging. However, producing large quantities of protein is extremely expensive, and we will need investors or an industrial partner in the future. The BHF could help us to find the right partner,” explains Professor Madeddu.
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I hope that the results of my work can make a difference in the lives of a lot of patients.
Helping older hearts Professor Madeddu is a cardiologist by background, and has been fascinated by the heart since he was a medical student. “Research requires a lot of determination and effort. I hope that the results of my work can make a difference in the lives of a lot of patients.” In 2021, around 12.5 million people in the UK were 65 or older. Life expectancy had been rising for decades, but the increases have slowed since 2010, and life expectancy for both men and women has fallen since the Covid-19 pandemic. Research like that of Professor Madeddu aims to help older adults stay healthy and independent for longer, which is among the UK Government priorities. “There is no current treatment to stop the heart’s ageing, and drugs used for heart disease can cause side effects in seniors,” explains Professor Madeddu. “We hope that giving older people a protein that is present in healthy centenarians, like those in Okinawa, helps their hearts work better for longer. Our approach proposes to increase health rather than simply combat disease. If we can find an effective treatment to delay ageing of the heart, we may be able to prevent serious disease in older people.”
Read the case report
Monica Cattaneo 1 , Antonio P Beltrami 2 , Anita C Thomas 3 , Gaia Spinetti 1 , Valeria Alvino 3 , Elisa Avolio 3 , Claudia Veneziano 2 , Irene Giulia Rolle 2 , Sandro Sponga 2 , Elena Sangalli 1 , Anna Maciag 1 , Fabrizio Dal Piaz 4 , Carmine Vecchione 4,5 , Aishah Alenezi 6 , Stephen Paisey 6 , Annibale A Puca 1 4 , Paolo Madeddu 3 The longevity-associated BPIFB4 gene supports cardiac function and vascularization in aging cardiomyopathy. Cardiovasc Res. 2023 Jan 13;cvad008. PMID: 36635236 DOI: 10.1093/cvr/cvad008.
Stem cell plasters to stop children needing repeated heart surgeries
Researchers at the University of Bristol, funded by the British Heart Foundation (BHF), have developed ‘stem cell plasters’ to revolutionise the way surgeons treat children living with congenital heart disease, so they don’t need as many open-heart operations.
Heart defects are the most common type of anomaly that develop before a baby is born, with around 13 babies diagnosed with a congenital heart condition every day in the UK. These include defects to the baby’s heart valves, the major blood vessels in and around the heart, and the development of holes in the heart.
Currently, for many of these children, surgeons can perform open-heart surgery to temporarily repair the problem, but the materials used for the patches or replacement heart valves are not completely biological and cannot grow with the baby. This means they can be rejected by the patient’s immune system which causes the surgical materials to gradually break down and fail in a few months or years.
A child might therefore have to go through the same heart operation multiple times throughout its childhood, which keeps them in hospital for weeks at a time, hugely impacts their quality of life and causes a lot of stress for the family.
Now, BHF Professor Massimo Caputo has developed the first type of stem cell patch to repair abnormalities to the valve in the large blood vessel that controls blood flow from the heart to the lungs, and to mend holes between the two main pumping chambers of the heart.
The stem cell plasters are designed to be sewn into the area of the child’s heart that needs repairing during surgery. The stem cells could then boost the repair of heart tissue without being rejected by the child’s body.
These patches have the potential to adapt and grow with the child’s heart as they get older, removing the need for repetitive heart surgeries and the many days at hospital recovering after each one.
There are around 200 repeat operations for people living with congenital heart disease every year in the UK. The technology could save the NHS an estimated £30,000 for every operation no longer needed, saving millions of pounds each year.
The BHF has awarded Professor Caputo nearly £750,000 with the aim to get these patches ready for testing in patients so clinical trials can start in the next two years, enabling more children and babies to benefit from the life-altering technology. The materials have already proven to work safely in animals.
The team is also in the early stages of developing other stem cell technologies using 3D bioprinting and gene therapy to one day be able to mend more complex congenital heart defects.
Massimo Caputo, BHF Professor of Congenital Heart Surgery at the Bristol Heart Institute, University of Bristol, said: “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 stem cell patches will be the answer to solve these problems.
“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.”
Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation, added: “If successful, this new stem cell therapy that acts like a healing plaster could revolutionise the results of heart surgery for children and adults living with congenital heart disease.
“It could offer a solution that means their heart is mended once and forever in a single operation, preventing people from facing a future of repeated surgeries and giving them the gift of a happier and healthier life.”
The work was partly funded by the National Institute of Health and Care (NIHR) Bristol Biomedical Research Centre (NIHR Bristol BRC), a partnership between University Hospitals Bristol and Weston NHS Foundation Trust (UBHW) and the University of Bristol.