2. Tissue Engineering Triumph: Lab-Grown Bladders
On April 15, the British medical journal The Lancet carried a landmark article showing that it is now possible to engineer a complex organ to replace one ravaged by disease. Anthony Atala, a surgeon and director of the Institute for Regenerative Medicine at Wake Forest University School of Medicine in Winston-Salem, North Carolina, reported that artificial bladders can be grown in the lab from a patient's own cells and successfully implanted. Over the past six years, seven children have received the organs, which are functioning well.
Atala's quest to build an artificial bladder began about 16 years ago when he was honing his skills as a pediatric surgeon at Harvard University. He became increasingly unsettled by a routine century-old procedure he was performing in young children: replacing damaged or diseased bladders with sections of the bowel or the stomach. Because the role of these tissues is to absorb chemicals (whereas the role of the bladder is to store and eliminate them), patients, especially young children, who underwent the procedure were often saddled with a suite of inescapable side effects. "When you replace bladder with intestine, you absorb chemicals you should get rid of, creating lots of problems," says Atala. Among them is a higher risk of cancer, stone formation within the walls of the transplanted tissue, and bone deformities due to calcium reabsorption by the tissue.
Atala wondered whether it would instead be possible to remove bladder cells from a patient and use them to grow a replacement organ, thus eliminating the risk of transplant rejection. "I had no idea how difficult it would be," says Atala. It took about a decade, but in 1999 he and his colleagues began implanting these engineered organs in spina bifida patients aged 4 to 19 who, in addition to spinal cord defects and nerve damage, had abnormal bladders.
For patient Kaitlyne McNamara of Middletown, Connecticut, who received her implant in 2001 at age 12, the timing could not have been more crucial, says her mother, Tracy McNamara. She had the "bladder capacity of a thimble," was wet all the time, and was forced to wear diapers. More critical was that her tiny, rigid bladder would spasm frequently, forcing urine back into her kidneys, where it triggered severe infections that were slowly destroying them. Her bladder condition disqualified her for a kidney transplant.
Six weeks prior to Kaitlyne's surgery, Atala and his team harvested a dime-size piece of tissue from her bladder, using this as the source of cells to create a new organ. A normal bladder has three layers: On the outside is muscle, in the middle is collagen, and the innermost layer consists of specialized urothelial cells that are impermeable to urine and protect the body from waste fluids. After a biopsy, Atala teased apart the three layers, cultivating the muscle and urothelial cells separately and discarding the collagen. Four weeks of cell division produced enough cells to build a new bladder. "The key to these technologies is, first and foremost, getting the cells to grow outside the body," says Atala. "Then you need to figure out how to attach them to a biodegradable scaffold."
Atala's method involved painting several coats of Kaitlyne's muscle cells on the outer surface of a bladder-shaped mold made of collagen. The inside of the scaffold was covered with her urothelial cells. The whole structure was then immersed in a nutrient bath and put in an incubator at 90 degrees Fahrenheit. Ten days later the bladder, looking like a shiny pink ball, was ready for implantation. Once in the body, if all went well, natural processes would take over and allow the tissue to mature. Five years after her implant, Kaitlyne lives without diapers, has normal bladder capacity, no longer suffers from kidney or urinary tract infections, and has a dramatically improved quality of life.
Critics caution that this is a small trial and that the implants need a longer follow-up. And technically, Atala has yet to create and implant an entire bladder; the ureters at the top and the sphincters at the base are still the originals. He is expanding clinical trials for the artificial bladder to include more populations who could benefit, such as bladder cancer patients. He is also working on engineering other body parts—the liver, nerves, heart valves, and pancreas. Next in line for clinical trials: blood vessels.