After severe heart failure, the ability of the heart to heal by forming new cells is very low. However, according to a recent study, after receiving treatment with a supportive heart pump, the capacity of a damaged heart to repair itself with new muscle cells becomes significantly higher, even higher than in a healthy heart.
The ability of the human heart to renew itself by regenerating its muscle cells, myocytes, is very limited. But until now, what happens to this capability when the heart is damaged by severe heart failure has been unknown.
Researchers at Karolinska Institutet in Sweden have now discovered that after an injury, the rate of cell renewal is even lower than in a healthy heart. Standard-of-care for patients with advanced heart failure is a surgically implanted pump that helps propel blood, a so-called left ventricular assist device (LVAD).
Kick-start the repair mechanism
Surprisingly, the researchers found that patients with such a heart pump, who have shown significant improvement in their heart function, can regenerate heart muscle cells at a rate more than six times higher than in healthy hearts.
“The results suggest there might be a hidden key to kick-start the heart’s own repair mechanism,” said Olaf Bergmann, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet and last author of the paper.
The mechanism behind the effect is still unknown and there is not yet any hypothesis to explain it.
“It is difficult to say. In the existing data we cannot find an explanation for the effect, but we will now continue to study this process at a cellular and molecular level,” said Bergmann.
The findings, published in the journal Circulation, open up the possibility of developing new therapies for patients with serious heart conditions that stimulate the heart’s ability to repair itself after damage. This way, patients wouldn’t have to rely only on heart transplants or other kinds of long-term mechanical support.
“This offers some hope that the recovery after a heart incident can somehow be boosted,” Bergmann added.
Determine the age of cells
It is generally difficult to determine the age of cells in the human body and to decide which cells are new and which are old.
However, by using a method earlier devised by Jonas Frisén, professor of stem cell research at Karolinska Institutet, the group has been able to count the rate of renewal of myocytes in the heart.
The method is based upon the fact that the percentage of radioactive carbon in the atmosphere, and subsequently in our cells, has steadily decreased since the nuclear test ban in 1963.
For every following year, there is a little less radioactivity in newly formed cells, which means that they can be ‘dated’.
Study details
A latent cardiomyocyte regeneration potential in human heart disease
Wouter Derks, Julian Rode, Sofia Collin et al.
Published in Circulation on 21 November 2024
Abstract
Background
Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.
Methods
We determined cardiomyocyte renewal in 52 patients with advanced heart failure, 28 of whom received left ventricular assist device support. We measured the concentration of nuclear bomb test–derived 14C in cardiomyocyte genomic DNA and performed mathematical modeling to establish cardiomyocyte renewal in heart failure with and without LVAD unloading.
Results
We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18 to 50× lower compared with the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart.
Conclusions
Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.
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