HEARTS CAN HEAL THEMSELVES: SCIENTISTS DISCOVER HUMAN HEART MUSCLE CAN REGROW AFTER A HEART ATTACK

WORLD-FIRST HUMAN STUDY FINDS HEART MUSCLE CELLS CAN DIVIDE AND REGENERATE AFTER A HEART ATTACK

SYDNEY, AUSTRALIA — A world-first study by researchers at the University of Sydney, the Baird Institute for Applied Heart and Lung Research and Royal Prince Alfred Hospital has challenged a long-standing understanding of the human heart, finding that adult human heart muscle cells can increase their rate of cell division after a heart attack.

The discovery provides new evidence that the adult human heart retains a previously underappreciated capacity to produce new heart muscle cells following injury and could eventually contribute to the development of regenerative treatments for people who suffer heart attacks and subsequently develop heart failure.

The research, published in the peer-reviewed journal Circulation Research, examined whether adult human cardiomyocytes — the specialised muscle cells responsible for contracting the heart — can respond to oxygen deprivation associated with a heart attack by entering the cell division process known as mitosis.

The study, titled “Human Hearts Intrinsically Increase Cardiomyocyte Mitosis After Myocardial Infarction,” was led by Dr Robert D. Hume of the University of Sydney and the Baird Institute, with Professor Sean Lal serving as senior author. The research involved a multidisciplinary team of scientists, clinicians, pathologists and researchers from institutions in Australia and the United Kingdom.

A FINDING THAT CHALLENGES A LONG-STANDING VIEW OF THE HEART

For decades, scientists have understood that the adult human heart has only a very limited capacity to replace heart muscle cells lost after injury. Unlike tissues such as skin and the lining of the intestine, which continually replace damaged cells, adult heart muscle has generally been regarded as having extremely limited regenerative capacity. A heart attack, medically known as a myocardial infarction, occurs when blood flow to part of the heart muscle is blocked. Without sufficient oxygen, heart muscle cells can become damaged and die.

The loss of these cells can weaken the heart’s ability to pump blood. Damaged areas may subsequently develop scar tissue, which does not contract like healthy heart muscle. The new study does not show that the human heart can completely repair itself after a heart attack. Rather, it demonstrates that adult human cardiomyocytes can increase mitosis and cytokinesis in response to ischaemia, meaning that some surviving heart muscle cells show evidence of entering the processes required for cell division. This distinction is scientifically important. The researchers are not reporting that a heart attack victim’s heart automatically returns to normal. Instead, the findings indicate that the human heart possesses a natural regenerative response that could potentially be strengthened through future medical therapies.

THE HUMAN HEART’S HIDDEN REGENERATIVE RESPONSE

The research focused on cardiomyocytes, the cells that make up the contractile muscle of the heart.

The investigators found evidence that these cells respond to ischaemic injury by increasing their participation in mitosis, the process through which one cell divides its genetic material in preparation for producing daughter cells. They also observed evidence of cytokinesis, the physical separation of a dividing cell into two daughter cells.

The researchers describe this as a significant finding because increased cardiomyocyte mitosis following a heart attack had previously been observed in animal models, including mice, but demonstrating the phenomenon in living human heart tissue represents a major step forward. The study therefore provides evidence that the human heart’s regenerative response may not be completely absent, as traditionally assumed.

Instead, the response appears to exist but may be insufficient to replace the large number of cells lost during a major heart attack.

THE BREAKTHROUGH CAME FROM LIVING HUMAN HEART TISSUE

One of the most important aspects of the research was the way the scientists obtained the tissue needed for their investigation.

The team used heart-tissue samples collected from consenting patients undergoing coronary artery bypass surgery at Royal Prince Alfred Hospital in Sydney. This enabled researchers to study living human heart tissue rather than relying exclusively on animal models, post-mortem tissue or laboratory-grown cells. The University of Sydney describes the approach as the first study of its kind to use tissue samples taken from living patients during bypass surgery to investigate this regenerative response. Samples were obtained from diseased and non-diseased regions of the heart, allowing researchers to compare tissue affected by disease or ischaemic injury with tissue that was not similarly affected. The tissue-collection method was developed through collaboration involving Professor Paul Bannon and Professor Sean Lal, who work across the University of Sydney, Royal Prince Alfred Hospital and the Baird Institute.

WHY THE DISCOVERY MATTERS

A heart attack can destroy a substantial proportion of heart muscle cells. The University of Sydney reports that heart attacks can eliminate up to one-third of the cardiomyocytes in the affected human heart. Although advances in emergency medicine and cardiovascular treatment have improved survival following heart attacks, surviving patients can remain at risk of developing heart failure. Heart failure occurs when the heart is unable to pump blood sufficiently to meet the body’s needs. In severe cases, transplantation may be required. This creates a major medical challenge because the number of people who could benefit from heart transplantation greatly exceeds the number of donor hearts available. The discovery that surviving human heart muscle cells can enter a regenerative process therefore raises an important research question: Can the heart’s natural regenerative ability be amplified sufficiently to repair damage after a heart attack? That is the question the research team hopes to address in future work.

FROM DISCOVERY TO FUTURE TREATMENT

Dr Robert Hume, the study’s first author, said the discovery changes the understanding of what happens inside the human heart following a heart attack.

The researchers’ longer-term objective is not simply to document the natural response but to identify ways of increasing it. If scientists can determine which biological signals cause surviving cardiomyocytes to divide and then safely enhance those signals, it may eventually be possible to develop therapies designed to stimulate the heart to produce additional muscle cells after injury. Such treatments could potentially reduce the loss of functioning heart muscle and lower the risk of progression to heart failure.

However, the researchers emphasise that this possibility remains a future therapeutic goal, not an available treatment. The natural regenerative response observed in the study is not strong enough by itself to prevent the serious consequences of a major heart attack.

PROFESSOR SEAN LAL: THE GOAL IS HEART REGENERATION

Professor Sean Lal, senior author of the research and a heart-failure cardiologist at Royal Prince Alfred Hospital, has described the ultimate objective as using the discovery to develop new heart cells capable of helping reverse heart failure. The availability of living human heart-tissue models gives researchers a platform for investigating potential treatments in human tissue before therapies are considered for clinical use. The University of Sydney reports that the research team has already identified several proteins in the living human heart samples that have previously been associated with heart regeneration in mouse studies. These findings could help researchers investigate whether biological pathways identified in animal research can be translated into treatments relevant to humans.

A NEW WINDOW INTO HUMAN HEART RESEARCH

The significance of the research extends beyond the immediate finding about cardiomyocyte division. The ability to study living human heart tissue provides scientists with an opportunity to investigate the molecular processes occurring inside the human heart following injury. Animal models remain essential to biomedical research, but biological processes observed in animals do not always behave identically in humans. The researchers therefore believe that living human tissue models could provide more accurate information for identifying possible regenerative therapies. This could accelerate research into the proteins, molecular pathways and cellular signals responsible for the heart’s regenerative response.

THE GLOBAL HEART DISEASE CHALLENGE

The significance of the discovery is amplified by the enormous global burden of cardiovascular disease. Cardiovascular disease remains the leading cause of death worldwide, making research into heart attacks, heart failure, prevention and regenerative treatment a major international scientific priority. The University of Sydney reports that heart disease remains a major health challenge despite improvements in cardiovascular treatment.

For patients who survive heart attacks but subsequently develop heart failure, the availability of treatments capable of restoring damaged heart muscle could represent a major shift in cardiovascular medicine. At present, however, the discovery should be regarded as an important scientific finding that opens a potential route toward regenerative treatment rather than as a cure for heart attacks or heart failure.

WHAT THE RESEARCH DOES — AND DOES NOT — PROVE

The findings provide evidence that adult human cardiomyocytes can increase their rate of mitosis and cytokinesis following ischaemic injury. The study therefore challenges the idea that adult human heart muscle cells are completely incapable of responding to injury through cell division. But the research does not demonstrate that a human heart can completely regenerate after a heart attack. It does not mean that a person who has suffered a heart attack can simply wait for the heart to repair itself. It does not provide a currently available regenerative treatment.

It also does not establish that stimulating cardiomyocyte division in patients would automatically restore normal heart function. Future research will need to determine how the process can be increased safely, whether newly produced cells mature and function normally, how they integrate with existing heart tissue, and whether increasing regeneration can improve long-term outcomes for patients.

THE ROAD AHEAD

The next stage of research will involve translating the biological discovery into potential therapeutic strategies. Scientists will need to identify the precise molecular mechanisms responsible for the regenerative response and determine how they can be manipulated without creating dangerous consequences.

Any future treatment would also need to demonstrate safety and effectiveness through extensive laboratory research and clinical trials before it could become part of routine medical care.

Nevertheless, the discovery provides an important new direction. Rather than viewing damaged adult human heart muscle as entirely incapable of regeneration, researchers now have evidence that the heart retains a measurable natural response that may be capable of being strengthened.

A SCIENTIFIC DISCOVERY WITH HUMAN CONSEQUENCES

For patients and families affected by heart attacks, the significance of the research is straightforward: scientists have found evidence that the human heart is not as biologically inactive after injury as previously believed. The heart may retain a limited capacity to produce new muscle cells, even after the damage associated with a heart attack. The challenge now is to understand that capacity and determine whether medicine can safely increase it.

For Dr Robert Hume, Professor Sean Lal, Professor Paul Bannon and their collaborators, the discovery represents the beginning of a new research pathway rather than the end of the search for a treatment. If future studies succeed in transforming this natural regenerative response into a safe and effective therapy, today’s finding could eventually contribute to a new generation of treatments designed not merely to manage the consequences of heart damage, but to repair the heart itself.

THE RESEARCH TEAM

The study brought together Robert D. Hume, Jessica Warwick, Woo Jun Shim, Cassandra Malecki, Mengbo Li, Lakshay Seth, Dylan Harney, Julien Dagher, Trina Lum, Geraldine Tierney, Wendy Cooper, Eugene Slaughter, Xiaosuo Wang, Lisa Nguyen, Louise Cole, James Edelman, Fairooj N. Rashid, Callum Houlahan, Antony Gao, Angela L. Ferguson, James J. H. Chong, Mark Larance, John F. O’Sullivan, Nathan J. Palpant, Paul Bannon and Sean Lal, together with other contributing researchers listed in the full journal record.

The research was conducted across institutions including the University of Sydney, the Baird Institute for Applied Heart and Lung Research, Royal Prince Alfred Hospital, the University of Queensland, the Walter and Eliza Hall Institute of Medical Research, NSW Health Pathology, the University of Western Australia and other collaborating institutions.