Bladders Grown in Biotech Lab Function in Dogs
Harvard scientists have grown replacement bladders in a laboratory dish and implanted them in dogs, a feat that could herald the beginning of a biotech revolution in solving the perennial problem of insufficient organ donors.
The bladders, implanted into six beagles, have functioned successfully for as long as 18 months so far, the team reports in the February edition of Nature Biotechnology.
The researchers grew bladder cells in the laboratory and then seeded them onto a bladder-shaped mold, where they proliferated and formed an organ.
Although more animal tests are necessary, trials in humans who have lost their bladders as a result of cancer, genetic disorders or infectious disease could begin within a couple of years.
The bladder is a rudimentary organ, much simpler than a liver or kidney, but the researchers’ success holds out promise that growing new tissues may eventually be a viable way to reduce the backlog of desperate patients waiting for replacement organs.
“The clear benefits of this method are the simplicity of the cell culture and the potential clinical efficacy” in humans, wrote Dr. Christian Lorenz of the University of Heidelberg, Germany, in an accompanying editorial.
Although the bladder is not a complex organ, it is more than just a simple bag that fills with urine. Unlike a balloon filling with water, the bladder must maintain a constant internal pressure as it fills--a relatively sophisticated process. If it doesn’t, fluids are forced into the urethra and the kidneys, producing a variety of damage. The bladder must also contract to void.
More than 400 million people worldwide suffer from some type of bladder disease.
An estimated 54,200 Americans develop bladder cancer each year, according to the American Cancer Society, and treatment often entails removal of the bladder. Many others lose their bladders as a result of congenital defects, infectious diseases, accidents, diabetes and heavy metal poisoning.
When the bladder is removed, surgeons must install a reservoir to replace it, even if urine is then drained into a colostomy bag outside the body. Usually, the reservoir is made from stomach or gastrointestinal tissue.
But that material cannot maintain pressure properly, and is designed for absorbing materials from fluids rather than for excreting them, so its use creates many problems, experts said. The tissue is also more susceptible to infections.
Bladders made of synthetic materials have also failed for the most part because they are incompatible with body tissues and become calcified, producing painful stones.
Bladder transplants are rarely performed because the risks associated with immunosuppressant drugs are greater than the risks associated with using stomach or gastrointestinal tissues.
Dr. Anthony Atala and his colleagues at Boston Children’s Hospital and Harvard Medical School reasoned that the need for immunosuppressive drugs could be eliminated if a replacement could be constructed using the patients’ own tissues.
Taking advantage of techniques developed during the last decade for inducing body cells to proliferate in the laboratory, Atala’s group harvested two types of cells from dog bladders: smooth muscle cells from the exterior of the bladder and urothelial cells that line the interior.
After producing large quantities of the cells in petri dishes, they scattered the smooth muscle cells onto the surface of a bladder-shaped scaffolding and the urothelial cells onto the interior. Each “neo-organ” was then implanted into the animal from which the cells had originally been obtained, after the dog’s own bladder had been surgically removed. The entire process requires about five weeks.
Within a month, the newly implanted organs had begun functioning properly and the biodegradable scaffolding had begun dissolving. Within six months, Atala said, the new bladders were fully functional and, in most cases, had a larger capacity than the animals’ original organs.
Atala refused to speculate about how soon scientists might attempt to implant neo-organs in humans, but he said that “we are taking a very hard look at that.”
Lorenz cautioned that there are still some potential problems to be considered. In cancer patients, for example, there is a risk that some malignant cells might be present among the cells used to construct the new bladder. That might lead to tumor recurrence.
He also noted that it is not yet clear how well cells from an elderly patient will proliferate.
But in patients with congenital defects or problems caused by poisoning or disease, he said, the technique could provide a very good solution to a vexing problem.
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Growing a Bladder
Researchers have grown replacement bladders that haved survived and functioned in dogs for up to 18 months. The synthetic organs could eventually help people who lose their bladders to cancer, disease or congenital defects.
1. To grow a replacement bladder, researchers harvest small quantitites of urothelial and smooth muscle cells from the bladder of the potential recipient.
2. Each type is allowed to proliferate in the laboratory, producing large numbers of cells.
3. The urothelial cells are then seeded on the inside of a bladder-shaped biodegradable mold, while the smooth muscle cells are seeded on the outside.
4. The synthetic bladder is then implanted into the recipient, where the cells continue to proliferate and the scaffold dissolves, leaving an intact bladder.
