By genetically manipulating cells to revert to a fetal-like state, scientists triggered the regeneration of heart muscle in adult mice.

Summary: Scientists have discovered a method to regenerate damaged heart muscle cells in mice by manipulating a gene to revert adult heart cells to a fetal-like state, which may offer new treatments for congenital heart defects and heart attack damage. The study, published in the Journal of Clinical Investigation, found that inhibiting the UQCRFS1 gene increases glucose utilization in heart cells, promoting cell division and growth.

Key Takeaways:

  • Regeneration of Heart Cells: Researchers found that inhibiting the UQCRFS1 gene in adult mice can regenerate damaged heart muscle cells by reverting them to a fetal-like state that utilizes glucose for energy.
  • Potential Treatments for Heart Conditions: This discovery may lead to new treatments for congenital heart defects like hypoplastic left heart syndrome in children and heart attack damage in adults by restoring the regenerative capabilities of heart cells.
  • Future Drug Development: The next step for researchers is to identify drugs that can trigger this regenerative response without genetic manipulation, potentially leading to non-invasive treatments for heart conditions.

Scientists have discovered a way to regenerate damaged heart muscle cells in mice, a development which may provide a new avenue for treating congenital heart defects in children and heart attack damage in adults, according to a study published in the Journal of Clinical Investigation.

Hypoplastic left heart syndrome, or HLHS, is a rare congenital heart defect that occurs when the left side of a baby’s heart doesn’t develop properly during pregnancy. The condition affects one in 5,000 newborns and is responsible for 23% of cardiac deaths in the first week of life.

Regenerative Potential of Cardiomyocytes

Cardiomyocytes, the cells responsible for contracting the heart muscle, can regenerate in newborn mammals, but lose this ability with age, says senior author Paul Schumacker, PhD, Patrick M. Magoon Distinguished Professor in Neonatal Research at Lurie Children’s and Professor of Pediatrics, Cell and Molecular Biology, and Medicine at Northwestern University Feinberg School of Medicine, in a release.

“At the time of birth, the cardiac muscle cells still can undergo mitotic cell division,” says Schumacker in a release. “For example, if the heart of a newborn mouse is damaged when it’s a day or two old, and then you wait until the mouse is an adult, if you look at the area of the heart that was damaged previously, you’d never know that there was damage there.”

Reverting Adult Cardiomyocytes to a Fetal State

In the current study, Schumacker and his collaborators sought to understand if adult mammalian cardiomyocytes could revert to that regenerative fetal state.

Because fetal cardiomyocytes survive on glucose, instead of generating cellular energy through their mitochondria, Dr. Schumacker and his collaborators deleted the mitochondria-associated gene UQCRFS1 in the hearts of adult mice, forcing them to return to a fetal-like state.

Observations and Findings

In adult mice with damaged heart tissue, investigators observed that the heart cells began regenerating once UQCRFS1 was inhibited. The cells also began to take in more glucose, similar to how fetal heart cells function, according to the study.

The findings suggest that causing increased glucose utilization can also restore cell division and growth in adult heart cells and may provide a new direction for treating damaged heart cells, Schumacker.

“This is a first step to being able to address one of the most important questions in cardiology: How do we get heart cells to remember how to divide again so that we can repair hearts?” says Schumacker in a release.

Future Directions: Drug Development

Building off this discovery, Schumacker and his collaborators will focus on identifying drugs that can trigger this response in heart cells without genetic manipulation.

“If we could find a drug that would turn on this response in the same way the gene manipulation did, we could then withdraw the drug once the heart cells have grown,” Schumacker says in a release. “In the case of children with HLHS, this may allow us to restore the normal thickness to the left ventricular wall. That would be lifesaving.”

The approach could also be used for adults who have suffered damage due to a heart attack, Schumacker says.

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