U.S. doctors have successfully implanted bladders grown in the laboratory into patients with bladder disease. These custom bladders grew from the patients' own bladder cells on a specially shaped mold. The surgeons hope to use the technique to repair or replace other complex internal organs.
Seven youths aged four to 19 are the first beneficiaries of new bladders engineered by Dr. Anthony Atala and colleagues at Wake Forest University in North Carolina. "In terms of actually engineering a complex construct that we engineer outside the body and then we implant inside the body, this is really the first time we have been able to do that," he said.
The youthful patients Dr. Atala treated had congenital bladder disease that caused unnaturally high pressures inside the organ. This problem can damage the kidney, which produces the urine passed by the bladder.
Traditional bladder reconstruction usually involves grafts from the small intestine or stomach. But the use of such tissue can cause complications because it is different from bladder tissue. Intestinal or stomach tissue absorbs liquids, while the bladder is designed to excrete them.
Atala's team took an alternative approach. They extracted bladder tissue from the seven young patients, and used it to grow muscle cells and bladder cells in the laboratory. They placed the cells layer by layer on bladder-shaped molds made from collagen, the main protein of connective tissue.
"This is done very much like baking a layer cake, if you will. After the mold is fully seeded, you are putting this into this incubator, which is like the oven. Seven weeks from the time you actually start with the small piece of tissue from the patient, it is ready to be implanted back into the patient," he said.
The Wake Forest University team reports in the journal Lancet that the engineered bladders were durable and functional through five years of follow-up without any off the ill effects associated with the older technique using bowel tissue. Since the organs are made from patients' own cells, their immune systems do not reject them as they might with organs transplanted from other donors.
Atala says his procedure did not replace the complete bladder in each patient, but a part of only the biggest, most bulbous portion of it excluding the neck. "If you can picture a light bulb, we would be replacing only a segment of the round portion," he said.
In a Lancet commentary, physician Steve Chung of the Advanced Urology Institute of Illinois praises the work as a milestone, but says engineered bladders will not replace the grafts of intestinal tissue until further studies with longer follow-up confirm these first results. He foresees the day when the technique could replace cancerous bladders.
Dr. Atala says his laboratory at Wake Forest University is studying the procedures for growing new bladders for possible use with other internal organs. "Currently we are working on several other projects, including regeneration of cardiac muscle, liver, pancreas, nerve, kidney, blood vessels," he said.
A U.S. company formed to market the bladder construction technique, Tengion, plans to apply later this year for U.S. government approval for larger clinical tests.