Milestone work helps 7 patients
By Carey Goldberg, Globe Staff | April 4, 2006

Researchers at Children's Hospital Boston have reconstructed the defective bladders of seven young patients using the patients' own cells, marking the first time that tissue engineering has rebuilt a complex internal organ in humans, a top medical journal reported yesterday.

The work is ''a really nice clinical milestone," said Dr. Robert S. Langer, a tissue-engineering pioneer at the Massachusetts Institute of Technology.

Someday, scientists believe, they will be able to routinely regrow failing organs using tissue engineering, which takes the patient's cells, cultivates them to grow along a scaffold that gives them the needed form, and then re-implants them where needed.

So far, researchers have focused on simpler pieces of anatomy such as skin. They have also fixed fingers using engineered bone, chest walls using engineered cartilage, and even major arteries. The bladder represents a next step: It is a relatively simple organ, often compared to a balloon, but nonetheless more complicated than these other tissues.

''In terms of actually engineering a complex construct that we engineer outside the body, and then we implant inside the body, this is really the first time we've been able to do that," said Dr. Anthony Atala of Wake Forest University in Winston-Salem, N.C., lead author of the research, which is published in today's issue of the journal Lancet.

The experiments did not replace the entire bladder, he acknowledged. But if you think of the bladder as a light bulb, his team replaced a large piece of the round part of the bulb, he said, and they ultimately hope to do the whole bulb. That will involve added challenges in hooking up the new bladder to the tubes that come down from the kidney, he said.

Atala, who was at Children's for years but recently moved to Wake Forest, serves on the board of directors of a company that has licensed patents based on the bladder tissue engineering, according to a financial disclosure in the Lancet.

In the experiment, surgeons took out a piece of each patient's bladder much smaller than a postage stamp. The cells were grown in a nourishing culture and placed along a scaffold that was molded much like a dome, said Dr. Alan B. Retik, surgeon-in-chief at Children's. Then, the dome-shaped structure was connected to the remaining bladder, which had been cut wide open to receive it, and together, the two parts made a ball-shaped organ.

The tissue engineers began with about 1 million cells taken from each patient's bladder, Atala said, and by the time they were ready to re-implant the new piece of bladder about seven weeks later, the engineered cells totaled 1.5 billion.

The seven patients in the study, whose ages ranged from 4 to 19, had been born with spina bifida, a spinal cord disease that harms the bladder as well. Without treatment, they faced possible damage to their kidneys brought on by faulty bladder function. After the operation, the patients reported significant improvement.

As before surgery, they still needed to use catheters to empty their bladders, but they gained two main advantages: They no longer had to worry about constant incontinence, and they faced less danger of kidney failure.

''They're more socially acceptable," Retik said of the patients, ''and I think ultimately it would be a boon for them, both their social and their work lives."

The technique could eventually help patients with a variety of severe bladder ailments and possibly even bladder cancer, Retik said, but is probably too extreme for the millions of women who suffer from typical ''stress incontinence," bladder weakness that causes occasional leakage.

Currently, patients with severe bladder problems usually undergo surgery to rebuild the bladder using tissue from the intestine, but such operations sometimes leave them with long-term problems, including metabolic imbalances and even cancer. The Lancet study was not designed to compare the intestinal technique with the tissue-engineering technique.

The tissue-engineering approach still needs extensive testing among other patients before it can be adopted as a substitute, according to a commentary that accompanied the Lancet article and was written by Steve Y. Chung of the Advanced Urology Institute of Illinois. For now, he wrote, using the intestine must remain the gold standard.

At the Wake Forest Institute of Regenerative Medicine -- and at other labs around the world -- researchers are working on engineering all kinds of other organs, including hearts. Their work holds out the hope of ending the drastic shortage in the supply of organs for patients who need transplants as well as providing future replacement parts for an aging population.

Atala said that he has already succeeded in engineering a sphincter muscle, and the institute is working on regenerating liver, pancreas, and kidney tissue, cardiac muscle, nerves, and blood vessels. The process of engineering the bladder was something like making a layer cake, he said, because it was necessary to grow different layers of cells and then incubate them so they would multiply.

The tissue engineering cost about $4,000 per patient, he said, though the entire treatment, including weeks of hospitalization, costs much more.

The Lancet paper was 16 years in the making, Atala said; the actual operations on the patients took place between 1999 and 2001, but it seemed critical to make sure that the improvements in bladder function, and the overall safety of the technique, lasted. Now, he said, he hopes that the technique can be tried on a wider variety of patients with defective bladders.

''We're happy because we've gotten this far," he said. ''But we realize at the same time that there are many other tissues and many other challenges ahead of us, so we have to keep focused and keep the course."

For one of the patients in the bladder study, 16-year-old Kaitlyne McNamara of Middletown, Conn., tissue engineering has led to a new kind of freedom, including freedom from diapers.

''Now that I've had the transplant, my body actually does what I want it to do," she told the Associated Press. ''Now I can go have fun and not worry about having an accident."

Carey Goldberg can be reached at goldberg@globe.com

Copyright 2005 The New York Times Company

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