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Pig hearts in humans?

Context: When he was a heart surgeon, David Cooper would have 140 patients referred to him for transplants each year; because of the shortage of donor organs, only about 25 would receive them. Now an academic researcher at the University of Pittsburgh Medical Center, Cooper is part of a broad effort to search for ways to use pig organs for human transplants.

Without extremely high levels of immunosuppressive drugs, pig organs seldom last for half an hour in, say, baboons. The organs swell up and turn black and must be removed quickly, or the animals may die. Cooper led a team of scientists from Harvard Medical School and Immerge Biotherapeutics in determining what would happen when hearts from pigs genetically modified to seem less “piglike” to a foreign immune system were transplanted into baboons.

Methods and Results: The baboon’s immune system targets the pig organs for attack mainly because of a particular sugar that covers porcine blood vessels. Three years ago, scientists created pigs unable to make this sugar by deleting a gene for a certain enzyme. Cooper’s team transplanted hearts from the genetically modified pigs onto the abdomens of eight baboons, where the researchers could tell how strongly the pig hearts were beating. Three baboons died for reasons other than organ rejection, and the hearts remained viable. In the other five baboons, the hearts stopped beating between 59 and 179 days after transplantation, at which time they were surgically removed. The small blood vessels in the organs were full of tiny clots, probably caused by a mismatch between tissues and blood-clotting systems. But the researchers found evidence that this clotting process can be at least slowed with anticlotting medicines, like aspirin. None of the baboons suffered serious infections as part of the study.

Why it Matters: Cooper and colleagues’ study marks the first transplant using pigs engineered to lack a gene and the first time xenotransplanted organs have survived for months when immunosuppressive drugs were administered in doses similar to those used in humans. It also marks the longest time a pig heart has survived in another species. In previous work, organ rejection has been inhibited, though not as dramatically, by using pigs engineered to contain human genes that protect their organs from the human immune system. Experiments using additional pigs with these human genes and without the pig sugar gene are planned, but the first pig-to-human transplants are years away, says Cooper. First, xenotransplants must be deemed as likely to help patients as other available treatments, like mechanical heart-assistive devices. Even then, concerns about ethics and infectious disease must be addressed.

Source: Kuwaki, K., et al. 2005. Heart transplantation in baboons using α1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nature Medicine 11:29–31.

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Tagged: Biomedicine

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