the Bladder is the first human organ ever grown in the lab and transplanted into patients

• my edits in bold
  
• 08 April 2006
• Peter Aldhous
• Andy Coghlan
• Roxanne Khamsi

IT IS being hailed as a landmark in tissue engineering. Seven youngsters who faced a future of incontinence and serious kidney problems have been given new bladders grown in the lab from their own cells, and grafted onto their existing bladders.

Researchers in regenerative medicine are impressed by the results, which were announced this week by Anthony Atala of Wake Forest University in Winston-Salem, North Carolina. "This is the first human organ ever grown in the laboratory and transplanted into patients," says Bob Lanza, head of scientific development at Advanced Cell Technology in Worcester, Massachusetts. "It's the beginning of a new medical era."

Maybe so, but tissue engineers warn that it will be years before they crack the problem of growing more complex, solid organs, such as kidneys and hearts. And Atala's technique does not yet match the results of conventional surgical treatment for severe bladder problems. "It's pioneering work," says Stéphane Bolduc, a paediatric urologist at Laval University in Quebec City, Canada. "But clinically, I'm not yet convinced."

In the late 1990s, while at Harvard Medical School in Boston, Atala replaced dogs' bladders with organs grown from scratch (New Scientist, 13 June 1998, p 16). This week, his team reported on seven people who were all born with spina bifida, which left them with shrunken bladders missing normal nervous connections. They were incontinent, and the fluid in their bladders was at dangerously high pressure, which can damage the kidneys. Between the ages of 4 and 19 they were given lab-grown bladders, and have now had the engineered organs for an average of four years (The Lancet, DOI: 10.1016/S0140-673(06)68438-9).

Atala and his colleagues first took a biopsy from each person's bladder, containing about one million cells. These cells were grown in culture for a month, until they had multiplied to around 1.5 billion cells, and were then seeded onto a sac-shaped "scaffold" made of collagen, a structural protein found in most of our tissues. In some cases this was mixed with polyglycolic acid, a biodegradable material used in surgical stitches. After being grown for a further two months, the engineered bladders were grafted onto the patients' own.

“The patients' cultured cells were seeded onto a sac-like scaffold of collagen and then grown for a further two months”

The usual treatment to fix defective bladders is to cut out a section of a person's small intestine and graft this onto the bladder. However, this can cause complications, including the secretion of mucus from the intestinal tissue into the bladder, which can lead to urinary infections and bladder stones. Atala's patients didn't have these problems, and their bladder function improved. In general, the organ's overall capacity went up and the pressure inside it went down. Rather than leaking urine almost continuously, the patients could remain dry for several hours at a time, although because they still lacked normal nervous connections, they did not gain full bladder control.

It is an encouraging start, says Bolduc, who is also working on tissue-engineered bladders. But he says the gains in capacity and reductions in pressure reported by Atala's team are still less than conventional surgery can achieve.

Atala admits that he still has some work to do. One goal is to grow a complete bladder, offering hope for cancer patients who must have the entire organ removed. This will require sophisticated surgery to connect the ureters, the tubes that carry urine from the kidneys. It also means growing the sphincter that normally seals the organ shut, opening only when we urinate. "We are actually making sphincter muscles now," Atala says.

Surgical tricks learned with these first bladders should help in future attempts to replace the entire bladder. Atala's best results came when he wrapped the grafts with omentum, a flap of fatty tissue that normally sits over the front of the intestines. It is rich in blood vessels, and seemed to help the grafts establish a blood supply.

Getting a good blood supply is also a key obstacle to researchers trying to grow solid organs, such as hearts and kidneys, and they must find a way to infuse nutrients into the growing structures.

From issue 2546 of New Scientist magazine, 08 April 2006, page 10