The first human recipients of laboratory-grown organs were by Anthony Atala, M.D., director of the Institute for Regenerative Medicine at Wake Forest University School of Medicine. In The Lancet, Atala describes long-term success in children and teenagers who received bladders grown from their own cells.
“This is one small step in our ability to go forward in replacing damaged tissues and organs,” said Atala, who is now working to grow 20 different tissues and organs, including blood vessels and hearts, in the laboratory.
The engineered bladders were grown from the patients’ own cells, so there is no risk of rejection. Scientists hope that laboratory-grown organs can one day help solve the shortage of donated organs available for transplantation. Atala reported that the bladders showed improved function over time – with some patients being followed for more than seven years.
The study involved patients from 4 to 19 years old who had poor bladder function because of a congenital birth defect that causes incomplete closure of the spine. Their bladders were not pliable and the high pressures could be transmitted to their kidneys, possibly leading to kidney damage. They had urinary leakage, as frequently as every 30 minutes.
The main goal of the surgery was to reduce pressures inside the bladder to preserve the kidneys. In addition, urinary incontinence, which was a problem before the surgery, improved in all patients.
“It is rewarding when you can see the improved quality of life in these patients,” said Atala.
The patients were candidates for a procedure to repair the non-functioning bladder tissue with tissue from the intestines. This 100-year-old procedure is also used to “build” bladders for patients with bladder cancer. But because the intestine is designed to absorb nutrients and a bladder is designed to excrete, patients who have the procedure are prone to such problems as osteoporosis, increased risk of cancer and kidney stone formation.
Atala had been working since 1990 to build bladders from patients’ own cells and in 1999 implanted the first organ in a patient. His current report discusses the long-term results with seven children who had the surgery.
“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 report involves children who were treated at Boston Children’s Hospital when Atala was director of the Tissue Engineering and Cellular Therapeutics at Harvard Medical School. In 2004, Atala’s program moved to Wake Forest.
The process for growing each patient’s organ began with a biopsy to get samples of muscle cells and the 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. Testing showed that the engineered bladders functioned as well as bladders that are repaired with intestine tissue, but with none of the ill effects.
“We have shown that regenerative medicine techniques can be used to generate functional bladders that are durable,” said Atala. “This suggests that regenerative medicine may one day be a solution to the shortage of donor organs in this country for those needing transplants.”
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.
Atala also directs the National Regenerative Medicine Foundation, which recently received $1 million from the federal government to create a Soldier Treatment and Regeneration Consortium to research how to treat burns and grow limbs for wounded soldiers.
Atala’s co-researchers on the bladder report are Shay Soker, Ph.D., and James Yoo, Ph.D., with Wake Forest, and Alan Retik, M.D. and Stuart Bauer, M.D., with Harvard.