From Our 2012 Archives
Doctors Report Historic Transplant in Child
In a Tissue-Engineering First, Doctors Think the Boy's New Windpipe Could Grow
By Brenda Goodman, MA
Reviewed by Louise Chang, MD
July 25, 2012 -- Ciaran Finn-Lynch is an accidental medical pioneer. With his life in danger, doctors used the 13-year-old's own stem cells to grow him a new windpipe, and they did it inside his body -- a feat that's never been accomplished before.
"It's a really heroic story," says Harald C. Ott, MD, an instructor of medicine at Harvard Medical School in Boston. "They really saved this kid's life."
Ott worked out some of the science that made the procedure possible but was not directly involved in Ciaran's treatment.
Two years after the surgery, doctors say Ciaran (pronounced KEER-an) is living the life of a normal teen. He's grown more than 4 inches and gone back to school. Best of all, he has no need for an expensive and complicated regimen of anti-rejection drugs.
What doctors are learning from his case could help thousands of children born each year with life-threatening birth defects.
An Urgent Medical Need Drives a Discovery
Ciaran was born with a windpipe so small and deformed that it caused his lungs to collapse.
Doctors managed to hold his airway open using metal tubes. But eventually the tubes eroded into his aorta, the large vessel that carries blood out of the heart. He was rushed to the hospital with massive bleeding. Twice.
The second time, the bleeding stopped on its own. That gave his doctors a small window of time to look for other options.
Two years earlier, scientists had devised a new way to create organs using a patient's own stem cells. Though the technique had only been tried in adults, they thought the same method might work for Ciaran.
Working quickly, his doctors located a trachea, or windpipe, removed from a 30-year-old Italian woman whose organs were donated after she died. The trachea was about the same size and shape needed to replace the deformed one that Ciaran was born with.
Scientists in Italy cleaned the organ of all its cells using a method discovered at Harvard Medical School. Working with a detergent found in shampoo, they were able to strip the cells away from the protein scaffold they grew on. It's a bit like remodeling a house by first tearing it down to the studs.
That step was important because it cleared away any markers that might have caused Ciaran's immune system to reject the transplant.
Back at Great Ormond Street Hospital, a children's hospital in London, doctors removed stem cells from Ciaran's bone marrow. Stem cells are uniquely flexible cells that can be coaxed to grow into nearly any kind of tissue. The cells were sent to a specialized lab to be purified and returned to the hospital the same day.
After surgeons sewed the stripped-down donor windpipe in Ciaran's chest, they coated it with his purified stem cells. They also injected the tissue scaffold with proteins that encourage cell growth. For good measure, they took tissue samples from Ciaran's own trachea and placed those inside the tube of the windpipe with the stem cells. The tissue samples acted like blueprints, giving the stem cells instructions for what they should become.
The 'Holy Grail' of Tissue Engineering: Organs That Grow
Ciaran's case, which is reported in The Lancet, is the first time doctors have rebuilt an organ inside the body. Normally, donor organs are washed, reseeded with stem cells, and then grown in a lab until they are ready to be used in a patient. The process takes several weeks.
"We did not have the time to engineer and to culture the cells in a bioreactor because this child needed to have something done quickly. We used the child, himself, as a bioreactor," says researcher Paolo De Coppi, MD, PhD, one of the surgeons who treated Ciaran. "For him, there was no other option."
Worldwide, just 12 tissue-engineered tracheas have been transplanted into patients. Ciaran is the first child to get one. Doctors are watching him closely to see if the new trachea will keep up with his growth spurts. Since he's already shot up more than four inches since the operation, doctors think there's a good chance it will.
"We believe the matrix of the transplant will remodel with time. So it should allow, when the child grows, for the transplant to grow with the child," De Coppi says.
About 3% of babies are born with organs or tissues that are so malformed they threaten the child's life or growth. About 2% of newborns have poorly developed windpipes or lungs.
If tissue-engineered grafts like the one Ciaran has could grow, doctors think the damaged parts could be replaced almost as soon as they're discovered.
"A lot of kids, like kids with heart defects, any sort of structural defect that needs repair, if you do a repair with something that doesn't grow with the patient, you're committing them to a series of operations," Ott tells WebMD.
"So the holy grail of tissue engineering is to come up with something that is so integrated into the human body that it grows with the human body," he says. "That would make a big difference."
SOURCES: Elliott, M. The Lancet, July 26, 2012. Ott, H. The Lancet, July 26, 2012. News release, Great Ormond Street Hospital. Harald C. Ott, MD, instructor of medicine, Harvard Medical School; researcher, department of surgery, Massachusetts General Hospital, Boston. Paolo De Coppi, MD, PhD, surgeon, department of surgery, Great Ormond Street Hospital, London.
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