Custom-made bladders produced from patients' own cells

Apr 4 2006

Scientists in the U.S. have produced custom-made bladders grown from patients' own cells which have been have been successfully transplanted and function well.

The team from the Institute of Regenerative Medicine at Wake Forest University in North Carolina say they have shown that regenerative medicine techniques can be used to generate functional bladders that are durable.

The bladders showed improved function over time with some patients being followed for more than seven years.

Lead researcher Dr. Anthony Atala, director of the Institute, says it suggests that regenerative medicine may one day be a solution to the shortage of donor organs for those needing transplants.

Seven patients were given new bladders engineered from a plug of tissue grown from their own, dysfunctional bladders and this meant they did not need to take drugs to prevent organ rejection, as do patients given transplants from either living or dead donors.

Atala's team has been working for 16 years to find ways to first identify and separate immature cells known as progenitor cells from the patients' bladders.

They then coaxed the cells to grow on a scaffold into the two main cell types found in bladders.

The patients, children and teens aged 4 to 19, 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.

Such patients often get bladders reconstructed from the intestines, but the procedure is imperfect because the intestine is designed to absorb nutrients and a bladder is designed to excrete; also patients who have the procedure are prone to such problems as osteoporosis, increased risk of cancer and kidney stone formation.

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.

Atala is a urinary surgeon and an expert in regenerative and stem cell science, he explains that the procedure began with three-dimensional CT scans, a computerized imaging analysis, to decide what the bladder shape should look like.

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.

Atala, who is now working to grow 20 different tissues and organs, including blood vessels and hearts, in the laboratory, says 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.

The report is published in the current edition of the Lancet.