In a landmark study, U.S. researchers say they have implanted the first laboratory-engineered bladders into children and teenagers whose own organs were defective — and grown them from the patients' own cells.
Cultivating tissue from a person's cells eliminates the risk of rejection, say the researchers from the Wake Forest University School of Medicine in Winston-Salem, N.C., who hope lab-produced tissue will one day relieve the shortage of donor organs available for transplant.
“This is one small step in our ability to go forward in replacing damaged tissues and organs,” said lead researcher Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest, who is now trying to grow 20 different tissues and organs — including blood vessels and hearts — in the lab.
The research involved seven patients aged four to 19, who had poor bladder function because of spina bifida, a congenital birth defect that causes incomplete closure of the spine and an abnormally formed bladder.
“The patients had decreased bladder pressures, which is an important component because these bladder pressures could rise to the point where they could cause kidney damage,” Atala said in a teleconference Monday from Winston-Salem.
To grow new bladder tissue, his team biopsied cells from the muscle and lining of the bladder walls in individual patients. These cells were cultured in the lab, then seeded onto a specially constructed, biodegradable mould, or scaffold, shaped like a bladder.
Over the next two months, the cells continued to grow into the mould, which was then sutured to the patient's original bladder. (The mould degrades as the bladder tissue integrates with the body.)
“These patients prior to surgery were usually having periods of wetness of up to every 30 minutes,” Atala said. “And after the surgery, their maximal periods of dryness were anywhere between three and seven hours.”
One of those patients is Kaitlyne McNamara, a 16-year-old from Middletown, Conn., whose spina bifida had affected the nerves that control the bladder, forcing her to have at least two surgeries and increasing her risk of kidney damage over time.
Her thimble-sized bladder and resulting incontinence also meant constantly wearing diapers.
But five years ago, Kaitlyne was referred to Dr. Atala, who grew tissue from her cells and implanted a lab-grown bladder. The change in her life has been dramatic, said her mother.
“She is diaper-free and planning to attend her junior prom in May,” Tracy McNamara said in an e-mail interview Monday. “Not being wet and having control of her personal habits has made her feel less different than her peers. It has increased her confidence level along with her self-esteem.
“To see her growth has been truly a parent's dream.”
Dr. Laurence Klotz, chief of urology at Sunnybrook Health Sciences Centre in Toronto, called the research “tremendously exciting.”
“I would say the principle that you can actually use bioengineered tissue to replace a human organ . . . is huge,” said Klotz. “It's important more in terms of what it heralds for the future than the implications for patient care right now.”
Currently, surgeons use a segment of a person's intestine to replace the bladder when it has to be removed, usually because of cancer. The surgery works “remarkably well” for adults with bladder cancer, most of whom are over age 50, he said.
But the procedure, known as intestinal cystoplasty, is less satisfactory for children, who have greater problems with reabsorption (intestinal tissue absorbs, while bladder tissue excretes) and are more prone over a lifetime to develop osteoporosis and kidney stones.
The technique could possibly be used for bladder cancer, Dr. Klotz said. “But the bowel works very, very well on those patients. And it's simple, you don't have to grow it. It's not at all clear that this would be superior to using bowel and it undoubtedly would be dramatically more expensive.
“So there may be more of an advantage in children.”
Dr. Atala said the cost of growing bladder tissue is about $4,000 US per patient.
In a Lancet commentary, Dr. Atala and his team were praised “for the milestone that they have reached.”
“But further multi-institutional studies are needed with longer follow-up,” wrote Dr. Steve Chung of the Advanced Urology Institute of Illinois. “Until then, intestinal cystoplasty remains the gold standard.”
Tests of the seven patients showed that the engineered bladders functioned as well as bladders repaired with intestinal tissue — but with none of the adverse effects associated with that procedure, which has been used for about 100 years.
The research, published online Tuesday by The Lancet, was begun when Dr. Atala was director of the Tissue Engineering and Cellular Therapeutics at Harvard Medical School in Boston. He implanted the first organ in a patient in 1999. In 2004, Atala's program moved to Wake Forest.
“We wanted to go slowly and carefully and make sure we did it the right way,” said Atala, who has followed some of his bladder-tissue recipients for almost seven years. “This is a small, limited experience, but it has enough follow-up to show us that tissue engineering is a viable tool that will allow us to tackle problems of similar magnitude.”
He said further study is needed before the approach could be adopted for widespread use.
