The children, ages 4 to 19, were born with defective bladders due to spina bifida and received replacement bladders between 1999 and 2001 at Children's Hospital of Boston, part of Harvard Medical School.

The technology, which holds promise for other organs including the heart, kidney, pancreas and liver, was developed by pediatric urologist Anthony Atala and colleagues formerly of Boston Children's and now Wake Forest University Institute for Regenerative Medicine, according to the April 4 online edition of The Lancet, a British medical journal.

Commercial Availability by End of Decade

Atala and his team are able to design an organ from scratch outside the body using a patient's cells and surgically implant it in the body where it continues to grow.

"This is the first time a complex replacement organ has been put into a human designed from the person's own cells outside the body," Atala said in a telephone interview.

The technology has been licensed to a King of Prussia, Pa., start-up firm, called Tengion Inc., which plans to submit an application to the Food and Drug Administration by mid-year and to begin its first clinical trials before the end of the year, said chief financial officer Gary Sender.

If all goes well, Tengion hopes to have the first bladders commercially available to children with dysfunctional bladders by the end of the decade.

No Rejection, No Need for Immuno-suppression Drugs

With thousands of patients in America waiting for organ transplants, the prospect of creating replacement organs, using a patient's cells, holds enormous potential.

Atala and 80 researchers at Wake Forest are developing the technology now for 20 different tissues and organs, including the kidney, blood vessels, heart, liver, pancreas and nerves, he said.

The children who received replacement bladders were followed for up to five years after surgery to make sure their bladders did not degrade and continued to function. The researchers reported the replacement bladders matured and grew in the body, without rejection or need for immuno-suppression drugs because the tissues used were the patients' own.

The children had "optimum bladder function" with no ill side effects, wrote Steve Y. Chung, a Spring Valley, Ill., urologist in a commentary in The Lancet.

"It is a huge feat, just brilliant work," Chung said of the research. Applying the technique to other bladder diseases, such as cancer, could be more difficult, requiring doctors to get the blood supply, ureters and uretha, and nerve signaling into an entirely new organ, Chung said. "We're not quite there yet. It's going to require a lot more investigation in animal studies."

Indistinguishable from Original Bladder

The surgery on spina bifida patients left a portion of the old bladder and sutured the new bladder onto it.

Atala, who is Tengion's scientific founder, developed the technology in 1990 and tested it for more than a decade in animals, including dogs whose urinary tracts most closely resemble humans.

Here's how a replacement bladder is made:

A bladder biopsy is obtained from the patient, then healthy urothelial and smooth muscle cells are grown in the lab. The cells are placed on a scaffold structure made of biodegradable material, like sutures, and left to grow for seven to eight weeks.

Next, researchers surgically implant the engineered bladder, which continues to develop in the body. The suturelike scaffold gradually dissolves, leaving only an organ that is structurally indistinguishable from a patient's original bladder.

An estimated 300,000 Americans have bladder cancer, including 60,000 new cases a year. Fewer than 2,000 patients a year undergo surgery for serious bladder problems caused by spina bifida and adult spinal cord injuries, Tengion said.

The main reason patients get replacement bladders is to relieve bladder pressure, which can lead to kidney failure. A benefit of the new bladders is improved continence, or urine leakage. Before getting new bladders, the children in the study had urine leakage every 30 minutes. After surgery, the interval was every 2 { to three hours or longer, researchers said.

'A Big Difference'

Tracy McNamara, a nurse in Middletown, Conn., whose daughter, Kaitlyne, 16, got one of the new bladders five years ago, said her daughter was "at a crossroads and had to have something done." Prior to the surgery, her bladder could hold a "thimble's worth" of urine. She wore a diaper and took a spare set of clothes, because she would often wet herself at school, soaking her clothes.

"Through the sixth grade, kids didn't want to play with her because she was wet and they didn't understand why," Tracey McNamara recalled. "The freedom this has given her. She's got this gorgeous gown for her junior prom. She would never have been able to wear it prior to the surgery."

Kaitlyne said Monday night that the surgery has made a big difference in her life. "Before I had the surgery, when I had accidents, kids made fun of me in school. It really hurt. Now I don't have that problem anymore," she said.

Atala and researchers have tested the new bladders in animals with bladder cancer, replacing the entire cancerous bladder with a new one "and it worked. We've not yet tested it in humans."

For spina bifida patients, whose bladders have shrunk and lack resiliency, surgeons slice open the old bladder and use it as a base to suture on the new one.

Traditional bladder reconstruction uses intestine and bowel tissue, which can cause serious side effects, including urinary tract infections, chemical imbalance, kidney stones, osteoporosis and even colon cancer.

"By using the patient's own bladder tissue, you are doing away with all those issues," Atala said.

Developed over 16 Years

While work in tissue engineering and regenerative medicine is a burgeoning field -- there are companies making replacement skin for burn patients and cartilage using human cells -- Tengion officials say they are unaware of another technology similar to Atala's.

The science behind Tengion was developed over 16 years and licensed in late 2003 by a Connecticut life-sciences advisory firm, Scheer & Co., which founded Tengion in early 2004.

Tengion's management team, led by CEO Steven Nichtberger, former head of global marketing for Merck & Co. Inc., has raised $39 million in venture capital and is in the process of raising "a minimum" of $35 million more, said Sender, the company's chief financial officer.

The firm, which has 50 employees, recently leased 45,000 square feet in a warehouse in Montgomery County, Pa., and plans to build a commercial manufacturing plant and locate its corporate offices there.

Tengion's science and technology operations are in Winston-Salem, N.C., where the company's two dozen scientists work closely with Atala. Tengion has built a pilot plant in North Carolina where the neo-bladders will initially be made for the clinical trials.

"It's groundbreaking science," Sender said. "Tengion is working with the Food and Drug Administration to try to bring this technology to patients. And we're hoping to repeat the success that Dr. Atala had."