Long-Term Success in Rat Leg Transplants Reported at UC Irvine

Times Staff Writer

In a medical breakthrough that could lead to limb transplants in humans, researchers at the University of California, Irvine, College of Medicine have announced that they have performed leg transplants on laboratory rats that have survived for long periods without rejecting the leg tissue.

The long-term survival of the transplanted limbs was achieved using a drug called cyclosporine, an immunosuppressant that has become increasingly popular among surgeons performing organ transplants in humans, officials said. Immunosuppressants work by preventing the body from rejecting transplanted tissues and generally must be used throughout the life of the transplant patient.

"A limb is considered a very hard organ to transplant," said Kirby Black, co-director of UC Irvine's reconstructive microsurgery and transplantation laboratories. "It is more difficult to keep the rejection from happening in a limb than it is in a kidney, for example. Until cyclosporine, if you tried the same treatments on a leg and a kidney, the leg would definitely reject and the kidney would probably not."

As a result, limb transplant surgery is still in the experimental stages and has yet to be done on humans. If a human finger is severed and it is saved, the digit can be sewn back on. But if the finger is lost, a donor's finger cannot be used to replace it.

Limb transplant experiments on animals have been done in the past, but with less success. Black and Charles W. Hewitt, the other director of the microsurgery and transplantation laboratories, are the first to use cyclosporine in such research.

"This research could spark a revolution in transplant surgery," Black said. "For the first time, we have shown that tissues of this kind can be transplanted for long terms of survival in animals. . . . On a relatively low dose of cyclosporine, we can keep these tissues alive. In the past, these tissues have been very difficult to keep alive after transplants using conventional drugs."

Dr. Eugene Lance, a professor of surgery at the University of Hawaii Medical School and one of the fathers of limb-transplant research, said the UC Irvine researchers' results are "very exciting . . . and have not previously been demonstrated."

But, Lance cautioned, the use of the drug on humans is still risky, in part because of its side effects.

"I think in the long run we'll have to refine our techniques a lot more before we can justify using immunosuppression for human conditions that are not life-threatening," he said. "Techniques have been available to us for quite some time to allow us to try complex tissue grafting, but the risks have always been too high."

Black and Hewitt have been working for six years and have done more than 300 operations transplanting the black legs of Norway rats onto all-white Lewis rats. Although the animals get feeling back in their new legs as soon as 30 days after the operation, the transplanted limbs are not fully functional, Black said. Some of the rats with transplanted legs have been able through retraining to regain partial ability to walk.

People, however, could possibly regain greater use of transplanted limbs through physical therapy. There are some roadblocks before Hewitt and Black's research can be used on humans.

Causes Kidney Damage

Cyclosporine, which was discovered in the mid-1970s by a Swiss scientist, does have side effects, cutting the body's ability to fight infection and causing some kidney damage.

"Cyclosporine is better than conventional immunosuppressants, though," Hewitt said. Although patients treated with the drug still run the risk of catching viral infections, they are less likely to catch bacterial infections.

"But we don't think this can be used in a non-life-threatening situation and lock the patient into lifetime use of the drug without (researchers) knowing more about it," Black said.

Although full limb transplants are a thing of the far future, the drug does have some immediate uses.

Skin Transplants

"Short-term skin transplants from cadavers can be done now on patients with massive burns to get them through the critical period when they face loss of life from the trauma," Hewitt said.

The drug can be used during the transplant, and when the patient's own skin begins to grow back, he said, the newly grown skin can be transplanted to the most seriously damaged burn sites in place of the donor's skin.

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