Rat's leg transplant avoids immunosuppressive drugs

November 09, 1990|By Susan Peterson | Susan Peterson,Orange County Register

IRVINE, Calif. -- Scientists at the University of California in Irvine have successfully transplanted the leg of one rat onto another rat without setting off an internal biological war.

The experiment was performed without the use of immunosuppressive drugs or radiation normally required in transplants to prevent tissue rejection.

The study has sparked a debate among immunologists, who are unsure whether it means that two immune systems worked simultaneously in the same animal, or what the results might mean for human transplants.

"Really, what we are doing is going right into the heart of the storm," said Kirby Black, professor of surgery. "We're letting two immune systems interact, and they should kill each other. But in this case, they did not."

Originally, Mr. Black and the other researchers hoped the rat experiment would yield new techniques of reconstructive plastic surgery. Instead, it might lead to major advances in the greatest enemy of transplant patients -- rejection of transplanted organs and tissue. It could have far-reaching implications for organ and bone marrow transplants and for severe immune system diseases such as arthritis.

The transplants, in which a hind leg was transplanted from one rat to another, should have failed, the researchers said; the limbs and their hosts should have rejected one another.

But Mr. Black and Charles Hewitt, another surgery professor at UCI, said almost 63 percent of the more than 20 rats that received the transplants lived healthy lives without any symptoms of rejection. Tests of the rats found that their bodies contained elements of both immune systems living in harmony.

The other rats developed signs of transplant rejection and died.

Other researchers caution that the experiments would have to be repeated -- with animals less genetically alike than the rats used in the UCI study and with smaller tissues -- before the finding could be considered confirmed.

"It's almost like cold fusion," said Gale "Morrie" Granger, a pioneer in immunological research at UCI. "It could be very real and important -- or it may just be an artifact of some system. The data may not be wrong, but it may be caused by something else we don't know about."

Dr. Winston Ho of St. Joseph Cancer Center, a specialist in bone marrow transplants, said the method was unlikely to work in humans, with their more complex immune systems.

Mr. Black said one reason the rats' transplants worked was that whole, live bone was transplanted. In standard bone marrow transplants such as those done in humans, marrow is sucked from bones and transfused into the recipient. The procedure is similar to a blood transfusion.

In the rat experiment, scientists took whole bone, with its supporting tissue, nutrients and helping cells, and grafted it onto the recipient.

A possible explanation is that whole bone contains specialized cells that suppress the immune system, Mr. Black said. "These suppressor cells could be like little anesthesiologists -- they put the cells that will normally fight to sleep," he said.

Dr. Vilas Likhite, a UCI immunologist and transplant surgeon, said he thought the experiment showed a "standoff" between two competitive immune systems.

"To perform a successful transplant without immunosuppression is quite profound," Dr. Likhite said. "It may lead to a better method of transplant -- but with people, we're talking about a . . . different ballgame."

"This is too dangerous to be tried clinically -- remember that a third of these rats did develop rejection and died," Mr. Black said. "But if we can take the mechanism apart and learn to manipulate it, then we may have a way of doing transplants without drugs or radiation."

In human transplants, rejection is controlled either by radiation that destroys the original immune system or by drugs that suppress the immune system. Both treatments put people at higher risks of infections and cancers.

Dr. Susan Ildstad of the University of Pittsburgh, a transplant researcher, said she found the experiments intriguing. They go to the heart of a puzzle that has fascinated researchers since the 1950s, when early transplant research indicated that closely related immune systems could combine and learn to tolerate each other, Dr. Ildstad said.

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