Scientists grow bladders from patients’ cells

In a major advance toward the development of artificial organs, bladders made by growing a patient’s own cells in the laboratory have been successfully implanted in seven children with spina bifida and shown to function for five years or longer, researchers announced today.

The achievement, reported online in the medical journal the Lancet, marks the first time that artificial organs more complicated than skin and bone have been implanted in humans. It brings much closer the day when scientists will grow new organs for people who have lost them to disease or injury. Clinical trials of the bladder-building process could begin this year. The team that invented it is using the same method to grow blood vessels, kidneys, livers and other organs – some of which have already been implanted in animals.

The bladder is a much simpler organ than a liver or a kidney, but the success of the artificial tissues in humans suggests that it may be possible to grow complicated organs and reduce the backlog of patients waiting for replacement organs.

An estimated 54,200 Americans develop bladder cancer each year, and treatment often entails removal of the bladder. Others lose their bladders as a result of congenital defects, diseases, accidents, diabetes and heavy metal poisoning.

Surgeons now replace the bladder by building a fluid reservoir using tissue from the bowel, but that produces many problems, including reabsorption of toxins, formation of stones, and kidney damage due to pressure buildup in the reservoir.

Dr. Anthony Atala and colleagues at the Wake Forest University School of Medicine have been working to overcome this problem by growing bladder cells in the laboratory, then seeding them onto a polymer scaffold shaped like a bladder.

They begin by removing a small piece of bladder, about half the size of a postage stamp. The tissue has three layers: muscle on the outside, a collagen supporting layer in the center, and specialized urothelial cells on the inside to hold the urine.

The team isolates the muscle and urothelial cells and grows them in the lab for about 30 days. The cells are not stem cells, but “progenitor” cells, which have the capacity to grow only into other bladder cells.

Meanwhile, using CT imaging of the patient to determine the size of the bladder, they construct a scaffolding of a biodegradable polymer. The muscle and urothelial cells are seeded onto the exterior and interior of the scaffold and the construct is grown in an incubator for two to three weeks.

Surgeons then remove scarred and diseased tissue from the patient’s own bladder and use the artificial tissue to rebuild the organ. As the final step, they wrap the new organ in omentum, a membrane from the interior of the abdomen rich in blood vessels that supplies nutrients and oxygen to the tissue until it can grow its own vessels.

Keeping the cells alive until they can establish their own blood supply has been the major impediment in past attempts to produce bladders. The omentum seems to have overcome this difficulty, said Dr. Tony Khoury, of the Hospital for Sick Children in Toronto.

The study’s patients all had spina bifida, the result of a birth defect that leads to incomplete closure of the spine. Their bladder tissue is hard, causing pressure to build up and be transmitted to the kidney, where it causes kidney damage. The patients also have urinary leakage.

“We have to make sure the vessels last a long time,” Atala said. “We’ve already shown that in animals, and now we have shown it in humans.”