Human Hearts Regrow Muscle After Heart Attack, Study in Circulation Research Finds
核心洞察
Researchers have demonstrated for the first time that adult human hearts produce new muscle cells after a heart attack, a phenomenon previously documented only in mice.
The finding, published in Circulation Research, relied on a world-first model using heart tissue collected from living patients during bypass surgery.
Cardiovascular disease (搜索) remains the leading cause of death worldwide, and a heart attack can destroy as many as one third of the cells in the human heart.
The adult human heart retains a limited but measurable capacity to generate new muscle cells after a heart attack, according to research published in Circulation Research — the first demonstration of the phenomenon in humans after it had previously been observed only in mice.
"Until now we've thought that, because heart cells die after a heart attack, those areas of the heart were irreparably damaged, leaving the heart less able to pump blood to the body's organs," said first author Dr. Robert Hume, from the Faculty of Medicine and Health and Charles Perkins Centre, and Lead of Translational Research at the Baird Institute for Applied Heart and Lung Research (搜索). "Our research shows that while the heart is left scarred after a heart attack, it produces new muscle cells, which opens up new possibilities."
Scientists had previously seen increased mitosis — the process by which cells divide and reproduce — in the heart muscle of mice following a heart attack. The new study is the first to show the same response in human hearts.
A Regenerative Response Too Weak to Prevent Damage
Hume cautioned that the discovery does not yet translate into a clinical benefit. "Although this new discovery of regrowing muscle cells is exciting, it isn't enough to prevent the devastating effects of a heart attack. Therefore, in time, we hope to develop therapies that can amplify the heart's natural ability to produce new cells and regenerate the heart after an attack," he said.
The heart's natural regenerative response is not currently strong enough to replace all of the muscle destroyed during a heart attack. Understanding how the process works, however, could help researchers find ways to strengthen it.
The Burden of Heart Attack and Heart Failure
Cardiovascular disease (搜索) remains the leading cause of death worldwide. In Australia, it accounts for nearly a quarter (24 percent) of all deaths. A heart attack can destroy as many as one third of the cells in the human heart, and although advances in treatment have dramatically improved survival over the past decade, surviving the initial attack does not always prevent serious long-term consequences.
Many patients eventually develop heart failure (搜索), in which the heart can no longer pump blood effectively enough to meet the body's needs. A heart transplant is currently the only cure, and it is available to only a small fraction of patients. Australia has approximately 144,000 people living with heart failure, while only about 115 heart transplants are performed each year — a major gap between the number of patients who could benefit from a new heart and the number of donor organs available.
Living Heart Tissue as a Research Platform
The research relied on a world-first approach using heart tissue collected from living patients during bypass surgery. These "pre-mortem" samples came from consenting patients undergoing heart bypass procedures at Royal Prince Alfred Hospital in Sydney, with researchers collecting tissue from both diseased and non-diseased areas of the heart. The sampling technique was developed by Professor Paul Bannon and Professor Sean Lal, who work jointly at the University of Sydney, Royal Prince Alfred Hospital and The Baird Institute.
Because the tissue comes from living human hearts, researchers can now study heart biology in a laboratory model that may more closely reflect what actually happens in patients.
Toward Therapies That Regenerate the Heart
The ability to collect and study living heart tissue could become an important tool in the search for regenerative treatments. The team hopes the model will help reveal how the heart produces new muscle cells and how that natural response might be strengthened.
"Ultimately, the goal is to use this discovery to make new heart cells that can reverse heart failure (搜索)," said senior author Professor Sean Lal, of the School of Medical Sciences and a heart failure cardiologist at Royal Prince Alfred Hospital. "Using living human heart tissue models in our work means that we will have more accurate and reliable data to develop new therapies for heart disease."
Lal added that research using these samples has already identified several proteins previously shown to be involved in heart regeneration in mice — a prospect the team now aims to translate to humans. Those proteins could provide clues about how to encourage damaged human hearts to generate more muscle cells. While such treatments remain a future goal, the study provides direct evidence that the adult human heart has at least some natural capacity to rebuild muscle after an attack.
A Separate Neonatal Pathway
In a distinct line of investigation, researchers at the University Hospital of Bonn (搜索) (UKB) and the University of Bonn have identified a previously unknown immune signaling pathway that helps newborn heart cells survive and regenerate after injury, with findings published in Cell Communication and Signaling (Springer Nature).
Unlike adult hearts, the hearts of newborn mammals can temporarily regenerate after damage, an ability that is rapidly lost within the first days of life. In a neonatal mouse model, the team found that three immune-related signaling molecules — CCL4 (搜索), S100A8 (搜索) and C1QA (搜索) — work together to activate a receptor called TLR2 (搜索) on heart muscle cells. Activation of this pathway stimulated heart cell proliferation, enhanced survival of heart muscle cells and reduced cell death.
"Our findings reveal an unexpected communication axis between immune signals and heart muscle cells that supports regeneration in the neonatal heart," said corresponding author Dr. Mona Malek Mohammadi, head of a research group at the Institute of Physiology I, UKB and the University of Bonn. "We were particularly surprised to find that TLR2 (搜索) acts as a central hub connecting inflammatory signals to regenerative responses."