US to run bedside trials with pigs livers

January 31, 1997

SCIENTISTS IN the United States are to use "humanised" pig organs to offer critically ill patients a last chance of life.

The transplantation of transgenic pig organs to humans - xenotransplantation - may still be some years away, but researchers at Duke University in North Carolina, are embarking on a clinical trial using genetically modified pig organs as a bridge between life and death.

Genetically modified pig livers will be used outside the body in a bid to maintain the life of a patient with acute liver failure until a human liver for transplantation can be found.

The primary obstacle to organ transplantation is the rejection of the transplant by the recipient's immune system. The more closely related the donor and recipient are, the less likely the transplanted organ will be rejected.

A spokeswoman for Duke University said the pig livers had been made more human by a microinjection of three human genes. By using a transgenic pig liver it is hoped that the chances of early stage organ rejection by the recipient will be reduced.

"We are attempting to fool the body's immune system," said the spokeswoman. "We want to make it believe that the organ is human, part of the patient."

The idea of using pig livers temporarily to replace failed human organs is not new. According to Roger Williams, director of the Institute of Hepatology at University College, London, the possibilities were first tried in the 1970s but high rejection rates and poor results meant the idea soon went out of fashion.

He said the pioneering work at Duke University, where genetically modified pigs' livers are to be used, is leading to renewed interest in the field.

The modified livers have so far been used experimentally to maintain life in baboons, but the human clinical trials are just getting underway.

The spokeswoman said that clinicians expected the trial technique would only be appropriate in selective cases, but may give enough time for a suitable transplant liver to be found or the patient's own liver to regenerate.

"These patients have to be really, really sick," she said. "If they don't have this they will die. But they have to be strong enough to cope with this procedure."

She said that in the ex vivo xenoperfusion procedure, as it is called, a catheter would be used to carry blood from the patient's leg to the pig liver, which would be located outside the body above the patient. The blood would then be returned to the patient in a circuit similar to that used in bypass surgery. The isolated pig liver would be kept functioning by a process which adds oxygen and nutrients to the human blood going through the liver.

The spokeswoman added: "It is a little like a kidney dialysis machine. The patient will have this for four to six hours, and then again 12 or 18 hours later over a period of three or four days until a human liver for transplantation is found. It is a bridge."

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