Rat Leg Transplants Succeed

In a medical breakthrough that could one day lead to limb transplants in humans, researchers at UC Irvine College of Medicine announced Monday that they have performed leg transplants on laboratory rats that have survived long-term 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.

‘Hard Organ to Transplant’

“A limb is considered a very hard organ to transplant,” said Kirby Black, co-director of UCI’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 people. If a human has a finger severed and saves the digit, it 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 Black and Charles W. Hewitt, co-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 in a telephone interview that the success of Hewitt and Black’s research with cyclosporine “is very exciting . . . and has not previously been demonstrated.”

Drug Still Risky

But Lance also cautioned that the use of the drug on humans is still risky.

“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. The animals take the cyclosporine in a mixture of Purina Rat Chow and peanut butter.

A rat’s life span is about three years, and the longest-lasting limb transplant took place on a rat called HT 115, which received the transplant at one year of age and died two years later, Black said.

Although the animals get feeling back in their new legs a 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 to regain partial ability to walk through retraining.

People, however, could possibly regain greater use of transplanted limbs through physical therapy. But there are some roadblocks before Hewitt and Black’s research can be translated into human uses.

Causes Kidney Damage

Cyclosporine, which was discovered in the mid-1970s by a Swiss research scientist testing soil samples for fungus, does have side effects. Because it is an immunosuppressant, it cuts the body’s ability to fight infection, and it also causes 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 such as cytomegalovirus --a herpes-type infection transplant patients are often victim to --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. “I am sure it would be unacceptable to use in a non-life-threatening situation now. But with regard to side effects, it is remarkably better than conventional immunosuppressants.”

Although full limb transplants are a thing of the “far future,” the researchers said, 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. Cyclosporine can be used during the short-term 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.

Further in the future, the researchers contend, surgeons will be able to transplant large blocks of tissue. For example, a patient whose jaw is partially removed because of oral cancer could have have a partial jaw transplant using cyclosporine to prevent tissue rejection. If a gunshot victim received a wound that left his hand intact but damaged the arm muscles controlling the hand, he could conceivably receive a muscle transplant, Black said.

The work of Hewitt and Black --along with a team of five other researchers--was published in the April edition of the medical journal “Transplantation.”