BOSTON — The once-fanciful dream of regrowing the heart and other failing organs has suddenly edged closer to reality: The first complex organ, the bladder, has been rebuilt in seven patients from living tissue cultivated in the lab.
“It’s really science fiction at its best,” marvels Tracy McNamara whose daughter got one of the first transplants and is living a more normal life because of it.
The breakthrough was reported online Tuesday in The Lancet medical journal where doctors explained how they mostly replaced diseased bladders from seven youngsters with tissue grown from the patients’ own cells. Though simpler tissues like skin and bone have been regrown and transplanted, this is the first time it has been accomplished with a more complex organ.
'Startling and exciting' advance
“It’s startling and exciting,” declared Dr. Eli A. Friedman, a transplant surgeon at SUNY-Downstate Medical Center in New York who was briefed on the findings.
“This suggests that tissue engineering may one day be a solution to the shortage of donor organs in this country for those needing transplants,” said Dr. Anthony Atala, the lead researcher.
Growing other organs will likely hold unforeseen challenges, however, since organs are so specialized in their functions, scientists stress.
Even for people with bladder disease — and there are an estimated 35 million in the United States alone — Atala’s technique requires testing on more patients and for longer times, researchers say. Replacing an entire bladder would pose many more problems, including reconnecting urine tubes, blood supply, and nerve signaling, according to Dr. Steve Y. Chung, an Illinois urologist who wrote a commentary for Lancet.
Still, he called the work “a tremendous, tremendous advance.”
Improved quality of life
For the children and teenagers in the study, the transplants reduced leaking from their bladders — a potentially big gain in quality of life. For 16-year-old Kaitlyne McNamara, of Middletown, Conn., the transplant has meant a new social life.
At the time of her surgery five years ago, her kidneys were close to failing as a result of her weak bladder. Now, they are working again, and she no longer wears a diaper. Instead, she was waiting for alterations on a low-cut champagne-colored dress for her junior prom.
“Now that I’ve had the transplant, my body actually does what I want it to do,” she said in an interview last week at her uncle’s house in Haddam, Conn. “Now I can go have fun and not worry about having an accident.”
The researchers at Children’s Hospital in Boston used a more mature cell type known as a progenitor. They first operated on the patients to remove bad tissue that made up more than half their bladders. They fished out muscle and bladder wall cells, seeded them on cup-like bladder-shaped scaffolds of collagen, then let the cells reproduce in the lab for seven weeks. Starting with tens of thousands, they ended up with about 1.5 billion cells. The cell-bearing molds were then surgically sewn back to the remnants of the patients’ original and partly working bladders, where the lab-nurtured cells kept maturing.
The team, which began its work in 1999, followed the last patient for almost two years. In undergoing the experimental procedure, the patients skirted the typical side effects of grafts that would otherwise have been made with their own intestinal tissue.
“It gives everyone in the field ... the evidence and encouragement they’ve needed to say this can be done,” said Dr. Stephen Badylak, a University of Pittsburgh expert in tissue engineering.
Atala, the research leader who has since moved to Wake Forest University, has already begun commercializing his transplant techniques through Tengion, a company he helped found in King of Prussia, Pa. It has licensing rights to patents on his work, and some of his research collaborators have acted as consultants.
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Some researchers were more cautious about the promise shown with the new procedure, saying the study lacks any direct comparison group of patients getting the traditional graft.
Dr. Joseph Zwischenberger, who edits the journal of the American Society of Artificial Internal Organs, questioned how well the new bladders worked in the first few patients and raised a “red flag” about two patients who left the study for personal reasons and were ultimately omitted from the results. He also said Atala’s attempts to commercialize the technique should add some skepticism toward the findings, which he nonetheless called “very interesting preliminary data.”
The patients in the study must still cope with the ravages of spina bifida, the birth defect that caused their bladder problems. Leaving the spine incompletely closed, spina bifida can turn off nerve signals that keep the bladder healthy. The stiff, leathery bladder leaks frequently, forcing the person to wear pads or diapers. What’s worse, the weakened bladders can flush urine back into the kidneys and damage them too.
The rebuilt bladders, though, were up to three times more elastic and better at holding urine, the researchers report. In all seven patients, kidney function was preserved, the study said. The patients must still empty their bladders regularly with a tube but can avoid leaking in between.
For Kaitlyne McNamara, the urinary infections, leaking, and daily diapers are now just embarrassing memories.
“It kind of boosted my self-esteem,” she says. “I don’t have to worry.”
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