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Lab-Grown Bladders Prove a Success in Dogs

By J. Travis

Foreshadowing a time when a patient's own cells may be harvested, multiplied, and fashioned into a replacement organ, researchers in Boston have successfully transplanted laboratory-grown bladders into six beagles.

"This is the first demonstration that you can engineer a complete organ and replace the native organ with [it]," says David J. Mooney of the University of Michigan in Ann Arbor, who is attempting to grow artificial livers.

For a century, physicians have replaced diseased or damaged bladders by removing sections of a person's intestines and shaping them into a substitute bladder. While the procedure offers some relief to patients, complications often develop because nature designed intestinal tissue for a purpose—absorbing nutrients—other than holding urine. "You start absorbing stuff that should be excreted," says Anthony Atala of the Children's Hospital in Boston.

Other physicians have turned to human-made materials to create artificial bladders, but those efforts have also run into problems. Consequently, to build a better bladder, Atala and his colleagues decided to employ the organ's own cells.

The bladder is essentially a hollow vessel with an outer layer of muscle cells and an inner lining of urothelial cells, which form an impermeable reservoir for urine. While bladder-muscle cells grow readily in the laboratory, urothelial cells have frustrated scientists for many years.

"The big step forward was finding the right soup—the right combination of growth factors—that would make these cells grow," says Atala. Indeed, he and his colleagues can now take a bladder sample no larger than a postage stamp and, within 6 weeks, grow enough urothelial cells to cover a football field.

To turn the cells into an organ, the researchers first mold biodegradable plastic into a bladder-shaped shell. They then coat the outside with layers of muscle cells and the inside with urothelial cells.

To test this strategy, Atala's group procured bladder tissue from beagles and grew it into organs. After removing the dogs' bladders, the investigators implanted the artificial ones derived from the beagles' own cells. Within a month, the organs began to perform like normal bladders, the researchers report in the February Nature Biotechnology.

Within 3 months, the plastic shells had degraded, and the transplanted organs were hard to distinguish from natural ones. Blood vessels quickly grew into them. Moreover, nerves seem to form proper connections with the new organs, allowing the dogs to regain normal control of their bladders. Some dogs have had the artificial bladders for nearly a year without any problems.

The beagles' recovery of bladder control was a pleasant surprise for Atala, who had expected that any dog receiving the artificial organ would need a catheter to drain away urine buildup. People with bladders made from intestinal tissue must use such catheters, he notes.

The new artificial bladders may prove useful for the many thousands of people whose own organ has been ravaged by cancer or damaged by an infection or injury. Even people born with defective bladders might have a healthy one grown from their own cells, says Atala.

While the bladders of dogs closely resemble those of people, Atala cautions that more testing of this transplant strategy must occur before artificial bladders are ready for the clinic. "If you're a dog with a bladder problem, you may be set, but it's always a significant challenge to translate things you can do in an animal model to things you can do in people," agrees Mooney.

References:

Lorenz, C., and B.M. Schaefer. 1999. Reconstructing a urinary bladder. Nature Biotechnology 17(February):133.

Oberpenning, F. . . . and A. Atala. 1999. De novo reconstitution of a functional mammalian urinary bladder by tissue engineering. Nature Biotechnology 17(February):149.

Sources:

Anthony Atala
Children's Hospital
Department of Urology
Laboratory for Tissue Engineering and Cellular Therapeutics
Boston, MA 02115

David J. Mooney
University of Michigan
Dept of Chemical Engineering
2300 Hayward
3074 H.H. Dow Building
Ann Arbor, MI 48109-2136

From Science News, Vol. 155, No. 7, February 13, 1999, p. 101. Copyright © 1999, Science Serv

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