To fix a heart, doctors train girl's body to grow new part

Four-year-old Angela Irizarry was born with a single pumping chamber in her heart, a potentially lethal defect. To fix the problem, Angela is growing a new blood vessel in her body in an experimental treatment that could advance the burgeoning field of regenerative medicine.

Doctors at Yale University here implanted in Angela's chest in August a bioabsorbable tube that is designed to dissolve over time. The tube was seeded with cells, including stem cells, that had been harvested from Angela's bone marrow. Since then, the doctors say, the tube has disappeared, leaving in its place a conduit produced by Angela's cells that functions like a normal blood vessel.

"We're making a blood vessel where there wasn't one," said Dr. Christopher Breuer, the Yale pediatric surgeon who led the 12-hour procedure to implant the device. "We're inducing regeneration."

Angela, who had little stamina before the operation, now has the energy of a regular kid. She is on several medications, but Breuer and her parents think she'll be able to start school in the fall.

Scientists have long been captivated by the ability of animals such as salamanders and starfish to regrow body parts lost to injury. It was long assumed that developmental forces that create a human being in the womb are lost at birth. But recent advances in stem-cell research and tissue engineering suggest that regenerative forces can be reawakened with strategically implanted stem cells and other tissue.

This notion is fueling research at many academic laboratories and dozens of start-up companies where scientists are hoping to identify effective ways to treat maladies including heart muscle damaged from heart attacks, paralysis due to spinal cord injuries and poor-functioning kidneys and bladders.

Angela's condition, known as hypoplastic left heart syndrome, affects some 3,000 newborns in the U.S. each year. With just one pumping chamber, or ventricle, instead of the usual two, the babies can't deliver sufficient levels of oxygen to their organs and extremities, compromising their development and causing them to turn blue and suffer from a lack of energy. Without a surgical repair, says Breuer, 70 percent of them die before their first birthday.

Pediatric surgeons typically treat the condition with a series of operations called the Fontan procedure, designed to enable the heart to function without the missing ventricle. The last operation involves implanting a synthetic blood vessel made of Gore-Tex to reroute blood from the lower extremities directly to the lungs instead of through the heart. The device works, but it is prone to clotting, infection and in some cases, the need for additional surgery later in life as the child grows. The idea behind Breuer's project is that a natural conduit with the biology of a normal blood vessel would grow with the child and avoid or significantly reduce complications associated with a synthetic tube.

Angela's case "is a real milestone and broadly important for the field of tissue engineering," said Robert Langer, a researcher at Massachusetts Institute of Technology and a regenerative-medicine pioneer who isn't involved in the Yale initiative. "It gives you hope that when you combine cells with a scaffold and [put] them in the body, they will do the right thing."

Angela's heart defect was diagnosed in utero, when her mother Claudia was five months pregnant. She had her first operation when she was 5 days old, and another at 8 months. But her heart defect was taking a toll. She was shy, small for her age and lacked the stamina of a normal 3-year-old.

"If she ran from [the living room] to the kitchen, she got tired and she had purple lips," her mother, Claudia Irizarry, a church secretary in Bridgeport, Conn., recalled.

Today, Angela seems more like a regular kid, said her father, Angel Irizarry, who works as a carpenter. "It's a huge difference," he said. "It's like going from a four-cylinder to an eight-cylinder car in one operation."Before the surgery, he added, "her eyes weren't as happy as [they are] now."

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