For the first time, researchers have created working artificial bladders in dogs. Experts say that the success, described in the February issue of Nature Biotechnology, has significantly advanced the prospect of repairing or replacing damaged human bladders with tissues grown from a patient's own cells.
About 7000 patients need bladder repair or replacement every year in the United States. These include babies with birth defects, elderly people who have lost normal bladder function, and those with bladder cancer, the fourth most frequently diagnosed cancer in white males. "Since you can't use plastic materials with bladders, we've been forced to look for living tissues," says William Steers, a urologist at the University of Virginia School of Medicine in Charlottesville. "Sometimes we use huge amounts of intestines to fashion a replacement bladder." But these procedures frequently cause complications.
After a 9-year quest, pediatric surgeon Anthony Atala and his colleagues at Children's Hospital and Harvard Medical School in Boston succeeded in growing large numbers of muscle and urothelial cells--specialized cells that coat the inside of the bladder--from tiny samples snipped from the bladders of dogs. After generating about 60 million cells (enough to cover about 3 square meters), the researchers used a pipette to paint the outside of a porous, bladder-shaped mold with muscle cells, and the inside with urothelial cells. "We apply one layer at a time, then put it in the incubator and let it cook," Atala says. The new organ is ready in about a week, when successive layers of cells have merged to cover both surfaces of the mold seamlessly.
The artificial organs began to work as soon as they were inserted into six beagles whose bladders had been removed. New blood vessels started to infiltrate within a month, the biodegradable polymer mold disintegrated by 3 months, and nerve endings penetrated the muscle by 6 months. The lab-grown bladders were still functioning normally when the 11-month experiment ended. Atala's team has now turned its attention to human transplants, although the first trial is still several years away.
"It's groundbreaking work," says Steers. "It opens up unlimited possibilities for replacement of internal organs, especially those that are muscular." However, he cautions that the organs may not work as well in older patients, and that problems with blood supply and nerve connections may arise. So, he says, "it's probably not quite ready for prime time yet."