GENETICALLY modified pig hearts have been successfully transplanted into baboons for the first time. The monkeys lived at least 90 days, suggesting the research could move onto human clinical trials. Eventually, the hope is that pig organs could help fill the gap between the need for transplants and a lack of donors.
Bruno Reichart at the Walter Brendel Centre of Experimental Medicine in Germany and his team used pig hearts modified to produce human proteins and to block carbohydrates that pigs have but primates don’t, both to reduce the risk of rejection.
They found that successful transplantation required blood to be pumped through the heart even when it was journeying from the pig’s chest to the baboon’s. Without that step, the first five baboons with pig hearts only survived for between a day and a month. In these animals, the left ventricle of the heart failed even after high doses of hormones were given to stimulate it.
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In the next group, of four animals, the team pumped a solution of glucose, hormones and red blood cells through the hearts from the time they were taken out of the pigs to their implantation in the baboons. One baboon was lost due to a technical failure, but the other three lived to 18, 27 and 40 days respectively.
When the team examined the hearts after the animals had died, they found that the organs in the second group had more than doubled in weight. That may be because pigs reach adult weight faster than baboons. “The heart must grow to support a fast-growing body, and the genes are not switched off when you transplant into a baboon. The pig heart thinks it is still in the pig, and it doubles its size within a month,” says Reichart.
To stop this, the team used a drug called repromicin, which blocks growth hormones. In the third group, of five baboons, that made the difference. Four of the five were healthy for 90 days after the transplant, which is when the experiment ended. The fifth was healthy for 195 days (Nature, ). Guidelines from the International Society for Heart and Lung Transplantation (ISHLT) say that 60 per cent of the animals in such a study should survive for 90 days before human trials.
These successful transplants had to be followed up with continuous intravenous infusions of the growth hormone blocker, though Reichart says humans could take it orally.
“Although the experiments achieved the survival guidelines suggested by the ISHLT in 2000, it is very likely that the national regulatory authorities will require longer survival today before approving a clinical trial,” says David Cooper at the University of Alabama at Birmingham, who helped lay out the guidelines.
He says that mechanical hearts are being used with increasing success, which may affect any decision on the use of pig hearts.
Reichart says a patient who has difficulties with a mechanical heart may be the first to get a pig heart. But before then, he says, we still need to genetically modify and breed pigs to reduce the risk of microorganisms being introduced into the human body via a transplant.
This article appeared in print under the headline “A step closer to pig organs for people”
