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Mending broken hearts: cutting-edge research finds clues to regenerating failing hearts

Can you mend a broken heart? Poets, writers and philosophers have long pondered the question. According to Conrad Epting, MD, a cardiac and pediatric critical care specialist at Lurie Children’s, the enthusiastic answer, biologically speaking, is: “yes, we can.”

“Many animals retain the ability to regenerate damaged heart tissue,” says Dr. Epting, whose research lab is studying the regenerative properties of cardiac stem cells. “It is largely a question of development, age and reprogramming.”

His research, conducted through the Stanley Manne Children’s Research Institute at Lurie Children’s, is informed by patients in the hospital’s Regenstein Cardiac Care Unit (CCU) and Lefkofsky Family Pediatric Intensive Care Unit. The CCU is the hub of Lurie Children’s Heart Center, whose cardiovascular-thoracic surgeons perform 450 heart surgeries each year, and boasts one of the nation’s best survival rates for corrective surgeries and heart transplants.

Dr. Epting says there are a number of challenges in treating children with progressive heart failure due to congenital heart disease. After undergoing surgery, many of these children will grow up to be healthy adults. However, children born with only a single ventricle (the heart’s main pumping chamber) or cardiomyopathy (an abnormal heart muscle) often develop progressive heart failure.

“As teenagers and young adults, many will experience decreased quality of life, and over a third will suffer premature death or the need for a heart transplant,” says Dr. Epting.

Turning back the clock: Epigenetic regulation

But what if cardiac stem cells could be reprogrammed to rebuild the damaged heart? According to Dr. Epting, zebrafish, which share many of the same genetic building blocks for heart development as humans, can repair the heart throughout their lifetime. However, in mice and humans, the “on” switch that enables stem cells to rebuild damaged heart tissue is switched “off” near the time of birth.

Scientists have discovered that stem cells taken from younger patients, or those exposed to chronic heart failure, have better regenerative properties. Dr. Epting believes that epigenetics—the process by which modifications to histone proteins help turn genes on or off—regulates the processes common to development, aging and our response to stress.

“Stem cells exposed to heart failure grow much better than cells taken from a healthy heart,” says Dr. Epting. “There are also more of them, and they show signs of being more youthful as if stress reverses aging. Being exposed to chronic heart failure somehow switches back on the heart’s developmental program to stimulate repair. By understanding this process, we may find a way to ‘turn back the clock,’ and trigger the heart to mend itself.”

Dr. Epting says that scientists used to believe that aging was just the accumulation of DNA mutations. “We now understand that aging reduces our ability to engage the youthful program because of epigenetic modifications,” he explains. “Learning how to reactivate this program will be one key to developing therapies that can heal the heart from within.”

Banking for the future of congenital heart disease

Dr. Epting developed the Lurie Children’s Cardiac Biorepository, saving excess tissue samples from more than 500 patients. He hopes this unique resource will stimulate translational research across the Heart Center. More recently, Dr. Epting pioneered the Fontan Futures® Initiative, the only program of its type in the United States. This program would enable expectant parents of babies diagnosed with only one ventricle to “bank” both stem cell-rich umbilical cord blood and atrial tissue from their baby’s heart. These would be frozen through the Mathews Center for Cellular Therapy at Northwestern Medicine on behalf of these children. “If heart stem cells can be saved during infancy when they are the most numerous, it may be possible to use these cells later to help these patients recover from heart failure by rebuilding their hearts using their own stem cells,” says Dr. Epting.

Dr. Epting’s research program is the only one in the country studying pediatric heart failure from an epigenetic perspective. His team is now collaborating with Ali Shilatifard, PhD, Chair of the Department of Biochemistry and Molecular Genetics at Northwestern University Feinberg School of Medicine, and an internationally recognized pioneer in epigenetics.

Philanthropy matters

Philanthropy has been instrumental to Dr. Epting’s research and the Lurie Children’s Cardiac Biorepository. Such support has made it possible for him to apply for funding from the National Institutes of Health and American Heart Association to further his lab’s discoveries.

“As a clinician, treating children with heart failure remains one of the biggest challenges we face,” he says. “By continuing our basic research with translational implications, I’m hopeful we can contribute to improving the lives of children struggling with heart failure.”

Dr. Epting’s research is funded by the Deitrich, Gadient and Rushmore families, the John and Lillian Mathews Regenerative Medicine Endowment, the Children’s Heart Foundation and the Mend a Heart Foundation, among others.

This article was originally published in the Spring 2016 issue of Heroes magazine.

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