Testing stem cells in tiniest hearts to fight birth defect

BALTIMORE (AP) — The 4-month-old on the operating table has a shocking birth defect, nearly half his heart too small or even missing. To save him, surgeons will have to totally reroute how his blood flows, a drastic treatment that doesn't always work.

So this time they are going a step further.  In a bold experiment, doctors injected donated stem cells directly into the healthy side of Josue Salinas Salgado's little heart, aiming to boost its pumping power as it compensates for what's missing.

It's one of the first attempts in the U.S. to test if stem cells that seem to help heart attack survivors repair cardiac muscle might help these tiniest heart patients, too.

"We think the young heart is able to be more responsive," said Dr. Sunjay Kaushal, chief of pediatric cardiac surgery at the University of Maryland Medical Center, who is leading the study in partnership with University of Miami researchers.

Kaushal bent over the baby's right ventricle, the part of the heart that will take over for the abnormal left side. The surgeon had repaired as much as possible for now. Next he measured where to place eight shots of precious stem cells.

Then the bustling operating room went silent as Kaushal helped fellow surgeon Dr. Si M. Pham guide tiny needles into the ventricle's muscle.

"We're not saying we're going to cure it," Kaushal said of the birth defect, called hypoplastic left heart syndrome. But, "my whole quest is to see if we can make these little kids do better."

Josue's parents knew there was no guarantee the experimental injections would make a difference. But their son had been hospitalized since birth and needed open-heart surgery anyway for a chance to go home. Teary-eyed, they clasped hands and prayed over Josue's crib moments before nurses wheeled him to the operating room.

"We are marching ahead with God," said Josue's father, Hidelberto Salinas Ramos, speaking in Spanish through a hospital interpreter.

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Nearly 1,000 babies are born with hypoplastic left heart syndrome in the U.S. each year. It's the most complex cardiac birth defect.

Josue is missing his left ventricle, the main pumping chamber that pushes oxygen-rich blood to the body. Other key structures on his heart's left side are too small or malformed to work.

Always lethal until a few decades ago, this defect now is treated with three open-heart surgeries performed between birth and age 3. Doctors route blood around the abnormal left heart and they convert the right ventricle — which normally would shuttle oxygen-poor blood to the lungs — into the main pumping chamber.

Today, about 65 percent survive at least five years, and many reach adulthood, said Dr. Kristin Burns, a pediatric cardiologist at the National Institutes of Health.

But too many children still die or require a heart transplant because the right ventricle wears out under its increased workload.

That's why doctors are conducting this early-stage study of whether stems cells might help that ventricle work better.

"This is very different than a surgical approach or giving a medicine just to treat the symptoms. This is trying to treat the underlying problem," said Burns, of NIH's National Heart, Lung and Blood Institute.

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"I know you're really nervous," Kaushal told Josue's father, placing a hand on his shoulder. "Everything is going to be fine."

Just 4 months old, Josue was undergoing his second open-heart surgery. The first operation, a day after his birth, was a temporary fix to keep his heart pumping and create an aorta, the main artery leading to the body, big enough for blood to flow. While he babbled happily at his family and nurses, Josue never got strong enough to be discharged to his Edgewater, Maryland, home. This time, Kaushal would take pressure off Josue's right ventricle — and inject those stem cells.

Even in adults, stem cell regeneration is highly experimental. But small studies involving heart attack survivors and older adults with heart failure have found what Dr. Denis Buxton, a stem cell specialist at NIH's heart institute, calls a modest benefit in how well their hearts pump blood.

For testing in babies, Kaushal turned to Dr. Joshua Hare at the University of Miami's Interdisciplinary Stem Cell Institute, who researches a specific type of stem cell donated from the bone marrow of healthy adults. Hare's institute freezes these so-called mesenchymal stem cells, which have a long safety record in adult studies, and is providing them free for the baby study.

Initially, Kaushal's team tested piglets, whose hearts are similar to humans. When the right ventricle was damaged, they found stem cell injections preserved the piglets' heart tissue. Apparently the cells spurred some of the heart's existing repair mechanisms.

Back in the Baltimore operating room, University of Miami researchers helped Kaushal's nurses thaw the frozen stem cells and prepare injections. A few feet away, Kaushal was moving a large vein so it will drain deoxygenated blood from the top of Josue's body straight to his lungs without having to enter that overworked right ventricle. (When he's 3, Josue will need a final operation to similarly reroute blood returning from his lower body.)

Then, just before his chest was stitched back up, Josue became the second baby with this defect to receive the experimental bone marrow stem cells.

It's an early-stage study that will compare 30 babies, half given stem cells, to see if the strategy is safe and shows any difference over surgery alone. If so, it could open stem cell research for other pediatric heart problems.

Other types of stem cells also are being explored for hypoplastic left heart syndrome. Mayo Clinic researchers have tested stem cells taken from affected babies' umbilical cord blood. Kaushal also plans to try stem cells from affected newborns' own heart tissue, something researchers in Japan are pursuing.

It will take several years to know if stem cell experiments work. But, like many babies after their second surgery for the heart defect, Josue bounced back — and a week later, finally got to go home.

By LAURAN NEERGAARD, AP Medical Writer

Copyright Associated Press. All rights reserved.

The Gayly - 12/20/2016 @ 11:03 a.m. CST.