By RON WINSLOW
New Haven, Conn.
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,"
says 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 Dr. 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 Dr. Breuer, 70% 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 Dr.
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," says 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., recalls.
In four meetings with Dr. Breuer and other Yale staff, they
discussed the pros and cons of the conventional synthetic tube versus the new
approach. A tissue-engineered version can still narrow or become blocked, for
instance, Dr. Breuer says. And more drastic complications such as cancer
triggered by stem cell therapy or a bad immune-system reaction can't be ruled
out. In the end, the choice to become the first patient in Dr. Breuer's study
turned on three things, Ms. Irizarry says: the family's faith in God, their
trust in the doctor, and the potential for a natural blood vessel that could
possibly help avoid more surgeries. "Before, they were using plastic, now
they're using this special graft that will grow with her," Ms. Irizarry
says.
Today, Angela seems more like a regular kid, says her father,
Angel Irizarry, who works as a carpenter. "It's a huge difference,"
he says. "It's like going from a four-cylinder to an eight-cylinder car in
one operation."Before the surgery, he adds, "her eyes weren't as
happy as [they are] now."
Development of the procedure has been painstaking. Dr. Breuer
undertook four years of laboratory research after he joined Yale in 2003 before
seeking approval from the U.S. Food and Drug Administration in 2007 to test the
approach on patients. It took four more years and 3,000 pages of data before he
got a greenlight. The study builds on the cases of 25 children and young adults
successfully treated in Japan a decade ago with a similar approach.
Dr. Breuer, who holds several patents through Yale related to the
technology, expects to implant a tissue-engineered blood vessel in a second
patient soon as part of a six-patient study to test the safety of the procedure
and determine whether the blood vessels actually grow in the body as a child
gets bigger. The hope is that if these patients are treated without a hitch,
the procedure may be available under a special FDA humanitarian device
exemption, which would allow Yale to charge for it while conducting a larger
study.
Write to Ron Winslow at ron.winslow@wsj.com
A version of this article appeared Mar. 20, 2012, on page D1 in some
U.S. editions of The Wall Street Journal, with the headline: To Fix a Heart,
Doctors Train Girl's Body to Grow New Part.
