Seven children doing well with laboratory-grown organs
Bladders were grown from the children's own cells
April 3, 2006
Three boys and four girls treated at Children's Hospital Boston are the first people in the world to receive laboratory-grown organs. The children, aged 4 to 19, received bladders grown from their own cells and have now been followed for an average of almost four years. Their cases are reported in the April 4th online edition of the journal The Lancet.
"This is one small step in our ability to go forward in replacing damaged tissues and organs," said Anthony Atala, MD (pictured above), who began working on the technology in 1990 as director of Tissue Engineering for the Urology Program at Children's Hospital Boston. Atala now directs the Institute for Regenerative Medicine at Wake Forest University School of Medicine.
In the United States alone, more than 10,000 children and adults undergo bladder replacement or repair surgery every year. Currently, the repairs are performed using tissue from the intestine or stomach. But because the intestine is designed to absorb nutrients and a bladder is designed to excrete, patients who have the procedure are prone to complications as osteoporosis, stone formation and occasionally cancer.
"The long-term problems with the use of bowel and stomach are significant and we've had no definitive answers," said surgeon Alan Retik, MD, Urologist-in-Chief at Children's Hospital Boston, and senior author of the Lancet study.
The study involved seven children who had poor bladder function because of spina bifida, a congenital birth defect that causes incomplete closure of the spine. Their bladders were not pliable and the high pressures made them vulnerable to kidney damage. They also had urinary leakage, as frequently as every 30 minutes.
The lab-grown bladders were implanted in nine children between 1999 and 2001, with the main goal of reducing pressures inside the bladder to preserve the kidneys. Two children were unavailable for follow-up, but tests in the other seven found that the lab-grown bladders functioned as well as bladders repaired with intestinal tissue, with none of the associated side effects. Urinary incontinence, which was a problem before the surgery, improved in all seven patients, and kidney function was preserved. Because the engineered bladders were grown from the patients' own cells, there were no problems with tissue rejection. Patients' outcomes improved as techniques were refined over time, the researchers reported.
"We wanted to go slowly and carefully and make sure we did it the right way," said Atala. "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."
The process for growing each patient's organ began with a bladder biopsy to get samples of the outer muscle cells and the urothelial cells that line the bladder walls. These cells were grown in a culture in the laboratory until there were enough cells to place onto a specially constructed biodegradable mold, or scaffold, shaped like a bladder.
The cells continued to grow. Then, seven or eight weeks after the biopsy, the engineered bladders were sutured to patients' original bladders during surgery. The scaffold was designed to degrade as the bladder tissue integrated with the body. Scientists hope that laboratory-grown organs can one day help solve the shortage of donated organs available for transplantation.
"We have shown that regenerative medicine techniques can be used to generate functional bladders that are durable," said Atala, who also directs the National Regenerative Medicine Foundation.
Atala said the approach needs further study before it can be widely used. Additional clinical trials of the bladders are scheduled to begin later this year at several centers, including Children's Hospital Boston.
Co-researchers on the bladder report are Stuart Bauer, M.D., of Children's Hospital Boston and Shay Soker, Ph.D., and James Yoo, Ph.D., with Wake Forest University School of Medicine.
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Founded in 1869 as a 20-bed hospital for children, Children's Hospital Boston today is the nation's leading pediatric medical center, the largest provider of health care to Massachusetts children, and the primary pediatric teaching hospital of Harvard Medical School. In addition to 347 pediatric and adolescent inpatient beds and comprehensive outpatient programs, Children's houses the world's largest research enterprise based at a pediatric medical center, where its discoveries benefit both children and adults. More than 500 scientists, including eight members of the National Academy of Sciences, nine members of the Institute of Medicine and 11 members of the Howard Hughes Medical Institute comprise Children's research community. For more information about the hospital visit: www.childrenshospital.org.
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