Complex organ re-engineered for bladder transplants

For the first time, US scientists have rebuilt a complex human organ, the bladder, using live tissue grown in the lab – a breakthrough that could hold exciting promise for one day regenerating ailing hearts and other organs.

Only simpler tissues – skin, bone, and cartilage – have been lab-grown in the past. This is the first time that a more intricate organ has been mostly replaced with tissue grown from the patient’s own cells.

“This suggests that tissue engineering may one day be a solution to the shortage of donor organs for those needing transplants,” said Dr Anthony Atala, the lead researcher. He said he believes the work provides a model for growing other tissues and organs.

The bladder transplants, performed on seven patients aged four to 19, were being reported online today in The Lancet medical journal.

The research team at Children’s Hospital in Boston did the first procedure in 1999, but wanted to make sure it would work on others. The results weren’t announced until the doctors did the other surgeries and followed the progress of the last patient for almost two more years.

“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.

Growing other organs will likely hold unforeseen challenges, however, since organs are so specialised in their functions, scientists stress.

Even for people with bladder disease – and there are an estimated 35 million in the US 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 signalling, according to Dr. Steve Chung, an Illinois urologist who wrote a commentary for The Lancet.

Still, he called the work “a tremendous, tremendous advance”.

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, 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 nappy. Instead, she was waiting for alternations on a low-cut champagne-coloured dress for her junior prom.

“Now that I’ve had the transplant, my body actually does what I want it to do,” she said last week near her home in Middletown, Connecticut. “Now I can go have fun and not worry about having an accident.”

Scientists, marvelling at how animals such as salamanders regenerate lost limbs, have long toyed with the futuristic possibilities of regrowing worn-out or injured human parts. Recent discoveries have transformed those hopes into an emerging reality.

Over the past decade, researchers began fashioning better scaffold-like platforms that hold growing cells and dissolve inside the body. The study of stem cells, which can mature into all the body’s other tissues, has also supercharged progress in regenerative medicine.

The Boston researchers 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 ‘scaffolds’ were then surgically sewn back to the remnants of the patients’ original and partly-working bladders, where the lab-nurtured cells kept maturing.

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.

Atala, who has since moved to Wake Forest University, has already begun commercialising his transplant techniques through Tengion, a company he helped found in King of Prussia, Pennsylvania. It has licensing rights to patents on his work, and some of his research collaborators have acted as consultants.

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 commercialise the technique should add some scepticism toward the findings, which he nonetheless called “very interesting preliminary data”.

The patients in the study like Kaitlyne McNamara 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 nappies. 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.