Stem Cells To The Rescue: Fixing Heart Defects In Children
MIAMI, Fla. (Ivanhoe Newswire) - More than 35,000 babies are born with a heart defect. For many, this means a lifetime of surgery and medicine. Now, for the first time, doctors are using stem cells to save their smallest patients and hopefully keep them off medication and out of the O.R.
Analiah runs the Duarte home, literally.
"I try to walk with her and she's like leave me alone," Johanna Duarte, Analiah's mom, told Ivanhoe.
She was born with one of the most lethal and rare congenital heart defects. It's called EbsteIn's anomaly, which means one of Analiah's heart valves failed to form.
"They're left with this horrible non-functional valve that allows blood to slosh back and forth inside their heart," Redmond Paul Burke, MD, Chief in the Division of Pediatric Cardiovascular Surgery at Miami Children's Hospital, told Ivanhoe.
Dr. Burke said it causes hearts to grow four, five, even six times larger than normal.
"Analiah was born with a heart that filled her entire chest," Dr. Burke said.
Previously, surgeons would repair, replace, or close her valve, but that surgery would need to be done over and over as she grows.
"The holy grail for heart valve repair and replacement is a valve that will grow with the child," Dr. Burke said.
Doctors created the valve out of extracellular matrix, a substance extracted from a pig's bladder. The implant acts like a fishnet. It captures stem cells flowing in Analiah's blood stream. The cells attach to the impact, grow around it, and create a new heart valve.
"We could see, for the first time in her life, the valve that we had created opening and closing," Dr. Burke explained.
A year later, Analiah's valve is working. As a result, her heart is now a third of the original size.
Dr. Burke said Analiah's new valve should grow with her throughout her life; so she would not need a transplant, drugs, or more surgery. He also believes this could be used in adults to replace heart valves.
BACKGROUND:Congenital heart defects are abnormalities in the heart's structure that are present at birth. About eight out of every 1,000 newborns have congenital heart defects. They happen because of an incomplete or abnormal development of the baby's heart during the early weeks of pregnancy. Some have been associated with genetic disorders, like Down syndrome, but the cause of most congenital heart defects are unknown. (Source: www.kidshealth.org)
SYMPTOMS: Congenital heart defects compromise the heart's ability to pump blood and to deliver oxygen to the tissues of the body. So, they often have telltale signs like:
- an increased rate of breathing or difficulty breathing
- a bluish color to the tongue, lips, and/or nail beds
- poor appetite or difficulty feeding
- abnormal heart murmur
- diminished strength of the baby's pulse
- sweating, especially during feedings
- failure to gain weight (Source: www.kidshealth.org)
EBSTEIN'S ANOMALY: Analiah Duarte had one of the most rare and lethal heart defects, called Ebstein's anomaly. It affects one in 200,000 U.S. births. In Ebstein's anomaly, the tricuspid valve, the valve between the chambers on the right side of the heart, doesn't work properly. Blood leaks back through the valve, making the heart work less efficiently. It can also lead to heart failure or enlargement of the heart. This heart defect occurs early in the development of a baby's heart. It is uncertain what risk factors cause the defect. Environmental and genetic factors are both thought to play a role. A mother's exposures to certain medications, like benzodiazepines or lithium, have been associated with Ebstein's anomaly in children. (Source:www.mayoclinic.com)
NEW TECHNOLOGY: Medical-biomaterial-company CorMatrix Cardiovascular, based in Georgia, had developed an extracellular matrix material, a collagen framework that cells could attach to and hold the organs together. It has the structure, shape, and signaling properties to attract stem cells. "If you put this sub-mucosal tissue anywhere in the body, it functions like a fisherman's net. It captures stem cells flowing through the bloodstream right where you want them. It's like having the framework of a house that can actually recruit all the bricks and wood need to create a perfect house," Redmond Paul Burke, MD, Chief, Division of Pediatric Cardiovascular Surgery at Miami Children's Hospital, was quoted as saying. The stem cells that are captured morph into the tissue needed for the malfunctioning organ to work properly. Previously, doctors would use the material to promote natural growth of human organs. Dr. Burke was the first to use it to fashion a baby's heart valve. Dr. Burke made a valve from the sub-mucosal lining of a pig's intestine. He sewed it in the place where the tricuspid valve would have been. The valve Dr. Burke made was anchored at two points: at the opening and on the other side that allowed the blood to flow into the right ventricle. When the right ventricle contracts, the slit closes and blood is pushed out the pulmonary valve. Doctors believe that the stem cells the matrix captures will help Analiah rebuild her own valve. They say it would eliminate the need for follow-up surgeries usually needed for children with an implanted valve. As the patient's heart grows, surgeons will need to replace the implanted valves with bigger ones. "Time will tell if her own valve has become her own living human valve," Dr. Burke was quoted as saying. (Source: www.http://www.miamiherald.com/2013/02/22/3247950_p2/a-baby-gets-a-second-chance-at.html#storylink=cpy)
Redmond Paul Burke, MD, Chief, Division of Pediatric Cardiovascular Surgery, Miami Children's Hospital, talks about a new stem cell treatment for heart valves.
When did you first met Analiah?
Dr. Burke: I first met Analiah when she was born in February of last year. Unfortunately, she was born with one of the most lethal and rare congenital heart defects, Epstein's Abnormality. Epstein Abnormality occurs when a baby's tricuspid valve fails to form, instead they're left with this horrible nonfunctional valve that allows blood to slosh back and forth inside their heart and their heart grows to enormous proportions. They essentially are born with a wall to wall heart that pushes their lungs aside and leaves them with no functioning lung tissue and a very poorly functioning heart.
Was that Analiah's heart? How big was her heart?
Dr. Burke: Analiah was born with a heart that filled her entire chest. It pushed her lungs to the side and all you could see when you looked at her chest x-ray was an enormous wall to wall heart. In most places in the world, Analiah would have been put in a corner of a nursery and allowed to die. However, in the United States there are multiple options for these children, unfortunately none of them are great. We can get these children through, but we're really just patching them along; we're not repairing their valve.
So, traditionally you would get Analiah a valve and then in five or so years you'd have to replace that valve again, correct?
Dr. Burke: Well our goal for a newborn baby with a problem with a heart valve would be to repair that valve and leave her with her own tissue so that she can grow. The Holy Grail for heart valve repair and replacement is a valve that will grow with the child. So she starts small and then over the first few years of life she'll quadruple in size. That means her valve has to increase in size with her. If I replace her valve as a newborn baby with a tiny mechanical valve, she'll outgrow it in months and she'll be back for another operation and then another and another. The amount of trauma that she'll endure over a lifetime is enormous. So, we're looking for a solution that will grow with her.
I read by the time she's 21 that she would have five or ten surgeries and each surgery there's a 50/50 chance. Is that correct?
Dr. Burke: The problem with these multiple operations in babies is that each operation is more dangerous than the last because the scar tissue keeps building up after every operation. So by the fourth, fifth, or sixth time back in to a baby's chest you're really in a dangerous territory and the baby might not make it off the table. You might not even be able to get the chest open safely. We really want a solution where we can go in and repair a newborn baby's heart and allow that repair to grow with her for the rest of her life.
Is that what you did for the first time ever with Analiah?
Dr. Burke: Well, Analiah was the first time we tried using extra cellular matrix. Extra cellular matrix is basically the frame work or the structure of a heart valve or the structure of an organ in the body. So, we actually took the extra cellular matrix from a pig's intestines shaped it in to a cylinder, which could function like a heart valve, and implanted that in Analiah's chest. Now we've been watching her for over a year to see if this will become a true functioning valve that's made out of her own cells.
Why does this material feel gauzy?
Dr. Burke: So, when you take this extra cellular matrix out of the package it feels like a sheet of rice paper. When you put it in water it softens up and it becomes very pliable. So, we use those characteristics to help us do the repair. We cut it to the exact dimensions of her heart while it was still a sheet of paper essentially. Then we sewed it together into a valve shape, then we put it in water and it became very soft and pliable. We then put that inside of her heart and anchored it to the critical locations where her normal valve should have been and then we watched to see if it would function.
Can you see the valve work right there on the table?
Dr. Burke: So, one of the great moments during Analiah's surgery was once we had implanted this new core matrix valve we started her heart up again and everyone in the room was anxiously waiting to see what the intra-operative echo would show. So the echocardiogram in the operating room was turned on at the completion of the procedure and then everyone watched the screen and we could see for the first time in her life the valve that we had created opening and closing inside of her right ventricle. The echo cardiologist looked up and said, "hey this looks good, this is working." I think everyone was thrilled that we may have done something that would save her life and offer hope to hundreds and thousands of other children throughout the world.
So could this replace heart valve replacement surgery?
Dr. Burke: As a heart surgeon I know I've got a certain number of options for repairing or replacing a valve. Analiah's valve was not repairable. So, if I had to replace it I could put in a mechanical valve, that would require that she takes a blood thinner and also the risk of a stroke or an infection in that valve for her whole life, one percent a year for her whole life. It would also require that I replace it as she outgrows it. All of that means trauma, morbidity and possible death. Tissue valves are another option for valve replacement, but in a baby tissue valves calcify at a radical rate and very soon after implantation they become incrusted with calcium. They essentially turn to bone and they don't function anymore. They're also not small enough to put in to a baby's heart the size of Analiah. So, we didn't really have that option. The only other option for her was to say okay we're just not going to use her right ventricle. We're going to throw it away and make her a one ventricle baby and we know those children have a much lower life expectancy. Our real desire for her was if we couldn't repair her valve, we would replace it with a valve that would grow that would not require anticoagulation.
Would this be a great option for a lot of people, even adults?
Dr. Burke: So, the idea of putting an extra cellular matrix inside the heart and having that matrix recruit stem cells from the patient and rebuild, essentially the patient rebuilds their own valve. We just give them the framework and then we let their cells create a new valve. We create the shape and the stem cells come in and finish the job for us. Then, that becomes the Holy Grail of a valve replacement because it will grow, it won't wear out, it won't require anticoagulation, and it's very unlikely to get infected. In a baby, a valve that grows saves that baby a lifetime of trauma.
Can you discuss how stem cells exactly work? Does it kind of catch them like a net?
Dr. Burke: Sure. So imagine that you implant a net inside the human body that is designed to capture stem cells. That's what extra cellular matrix does. Imagine that you can implant a net inside the human body that will capture stem cells and re-grow an organ in the right spot that functions like a normal human valve. That's what this technology is offering us the possibility for. We can implant a net that captures stem cells that turn into a functioning human valve.
How do the stem cells get there?
Dr. Burke: We have stem cells circulating through our body every moment of every day. They are what help us heal, overcome inflammation, tissue destruction, and tissue damage. If we could really control the stem cell process, we could essentially achieve eternal youth. Stem cells are really the key to how we repair our bodies. Our bodies are damaged every day and our stem cells can come in and repair that damage.
What's your hope for Analiah?
Dr. Burke: So, Analiah is growing and thriving. Her mother is really happy. I can tell when she's holding her the smile on her face is the most beautiful thing you could ever see. Analiah is a very happy baby and my hope for her is that this valve will grow with her and that I won't ever have to reopen her chest, and she won't ever have to be in the operating room again. Now, that is possible. Right now what we're seeing is she's doubled in size and her valve seems to be growing with her.
FOR MORE INFORMATION, PLEASE CONTACT:
Miami Children's Hospital Heart Program