Scientists at the Stanley Mann Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago have discovered a way to regenerate damaged heart muscle cells in mice, a discovery that could lead to new avenues for treating congenital heart disease in children and damage caused by heart attacks in adults, they report in a study published in the Journal of Clinical Research.
Hypoplastic Left Heart Syndrome (HLHS) is a rare congenital heart defect that occurs when the left side of a fetal heart does not develop properly during pregnancy. It affects 1 in 5,000 newborns and is responsible for 23% of cardiac deaths in the first week of life.
Cardiomyocytes, which are responsible for heart muscle contractions, can regenerate in newborn mammals but lose this ability as they age, said senior author Paul Schumacher, PhD, the Patrick M. Magoon Distinguished Professor of Neonatal Research at Lurie Children’s Hospital and professor of pediatrics, cell and molecular biology and medicine at Northwestern University Feinberg School of Medicine.
“At birth, cardiomyocytes are still able to undergo mitosis,” says Dr. Schumacher, “so if you damaged a newborn mouse’s heart a day or two after birth, for example, and then wait until the mouse is an adult and look at the previously damaged parts of the heart, you’d never know that damage was there.”
In the current study, Dr. Schumacher and his collaborators sought to elucidate whether adult mammalian cardiomyocytes could revert to a regenerative fetal state.
Because fetal cardiomyocytes rely on glucose to survive instead of generating cellular energy through mitochondria, Dr. Schumacher and his colleagues deleted the mitochondria-related gene UQCRFS1 in adult mouse hearts, reverting the mice to a fetal-like state.
In adult mice with damaged heart tissue, the researchers observed that when UQCRFS1 was inhibited, heart cells began to regenerate. The cells began to take up more glucose, similar to the function of fetal heart cells, according to the study.
Dr Schumacher said the findings suggest that increasing glucose utilization may also restore cell division and growth in adult heart cells, potentially providing a new direction for treating damaged heart cells.
“This is the first step toward answering one of the most important questions in cardiology: how do we teach heart cells how to divide again so we can repair the heart?” Dr. Schumacher said.
Building on their findings, Dr. Schumacher and his collaborators will now focus on identifying drugs that can induce this response in heart cells without genetic manipulation.
“If we could find a drug that activates this response, similar to genetic manipulation, we could stop the drug once the heart cells have grown,” says Dr. Schumacher. “In children with HLHS, this could potentially restore left ventricular wall thickness to normal, which could be life-saving.”
Dr. Schumacher said the treatment could also be used in adults with damage from a heart attack.
This research was supported by National Institutes of Health grants HL35440, HL122062, HL118491, and HL109478.
Research at Ann & Robert H. Lurie Children’s Hospital of Chicago, conducted through the Stanley Mann Children’s Research Institute, is focused on improving children’s health, transforming pediatric care and ensuring a healthier future through a relentless pursuit of knowledge. Lurie Children’s Hospital is a nonprofit organization committed to providing excellent care to every child. U.S. News & World Report ranks the hospital as one of the top children’s hospitals in the nation. Lurie Children’s Hospital is the site of pediatric training for Northwestern University Feinberg School of Medicine.
