Thanks to advances in the diagnosis and treatment of congenital heart disease, babies born with heart defects live longer than ever. Yet, despite substantial progress, many continue to face bleak odds, lifelong medication, multiple surgeries and progressive heart failure, often requiring a transplant.
But what if instead of a heart transplant, a child's own cells could be coaxed into healing the heart from within? What if stem cells saved after delivery could be injected into a child's failing heart later on to help regenerate its function and boost its pumping ability?
‘Heart failure, a disease of the heart muscle, or structural heart disease, causes stress that induces stem cells to initiate repair, mimicking the process of building the heart that occurs in the fetus and the in the newborn.’
AdvertisementCardiac critical care physician Conrad Epting, M.D., is on a mission to answer these questions.
Harnessing the body's own defenses
Call it the body's way of coping with injury: Cells under stress act younger and multiply faster, Epting says.
The classic example of this self-defense mechanism is damage to the muscle induced by strenuous exercise. As a result, muscles get bigger, stronger, more elastic and healthier. It''s a process that happens in all tissues except the heart and the brain. But recent research suggests that the stress of heart failure may be one notable exception. Studies have found that stem cells obtained from failing hearts act younger, are more vigorous and multiply faster than cells obtained from healthy hearts.
What if this intrinsic self-repair mechanism could be turned into a therapy to mend broken hearts?
The working hypothesis, Epting explains, is this may be nature's way of trying to avert catastrophe: When a baby's heart begins to fail, the organ goes into overdrive, cranking out more stem cells in an attempt to save the damaged heart muscle.
"We believe that heart failure, whether caused by cardiomyopathy, a disease of the heart muscle, or structural heart disease, causes stress that induces stem cells to initiate repair, mimicking the process of building the heart that occurs in the fetus and the in the newborn," Epting says. "If we can capitalize on that, we can reengineer heart tissue or trigger reparative stem cells to halt the disease process."
In other words, cardiac cells from ailing hearts may have greater healing potential. These cells, Epting says, also have longer telomeres - protective caps at the end of our chromosomes believed to guard DNA vitality and gene health.
"Our care in pediatric heart failure is mostly supportive," Epting says. "We can give kids medication, defibrillators and eventually heart transplants but many of them still get sicker and die. We're looking to change that by helping hearts to heal from the inside."
The road ahead
Scientists have yet to understand how the cellular switch regulating the ability of the heart's own stem cells to repair damage turns off near the time of birth. Understanding what that switch is and how to turn it back on may be a key to stimulating heart regeneration. Understanding the malfunctions inside heart cells that culminate in the development of full-blown heart disease is also poorly understood. Unraveling the shifts in cardiac cell behavior might pave the way to therapies that obviate the need for surgery and transplants and help sustain, even regenerate failing hearts.
Scientists' ability to do so is predicated on access to well-preserved heart cells and heart tissue. Historically, Epting says, access to human samples has been a major barrier to moving research forward. To tackle this problem, Epting and team have created a biorepository for excess heart tissue removed at the time of surgery to help fuel research on stem cells and heart failure.
In addition, Lurie Children's is creating a blood cord and heart tissue bank from newborns diagnosed with critical forms of heart disease. These samples are deep-frozen and stored for future use in the hopes that as babies with heart disease grow older they might benefit from emerging therapies to mend their failing hearts. Such therapies, Epting says, may include stem cell injections to replace scar tissue in the failing heart, or perhaps, even replacement of missing heart chambers using 3-D printed ones.
Lurie Children's scientists are collecting and studying cardiac tissue from babies with a range of congenital heart conditions, including structural heart defects, diseases of the heart muscle (cardiomyopathies) and disorders of the electrical system of the heart that lead to rhythm disturbances.
The research focuses on several key areas:
- understanding what cells and genes in the heart respond to heart failure
- understanding what factors regulate these genes
- pinpointing the time and mechanism of the "off switch" that controls whether heart cells can divide so that regeneration can be stimulated to halt heart failure in its tracks
- comparing stem cells obtained from healthy and diseased hearts to unravel differences that may reveal key molecular events driving heart disease
Thus far, the repository has collected 800 samples from 515patients. The samples are accessible to researchers at Lurie Children's and nationally through Epting''s collaborative network and the Congenital Heart Surgical Society.
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