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Engineered pig organs survive in monkeys

December 8, 2003 By Helen Pearson This article courtesy of Nature News.

Humanized kidneys appear to thwart first round of rejection.

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Genetically modified pig kidneys have survived long after being transplanted into baboons. Researchers hope that this early success may pave the way for animal-to-human organ transplants.

The pigs used in the experiment were engineered to have human-friendly organs in 2002. They lack a key sugar molecule that normally prompts the human and monkey immune system to launch an aggressive and fatal attack on foreign tissues.

Now David Sachs, of Massachusetts General Hospital in Cambridge, and his team have transplanted kidneys from the genetically modified pigs into eight baboons. The new organs enabled the animals to survive for up to 81 days, compared with around 30 days for non-transgenic kidneys.

The results show that, in principle, the genetically engineered pig organs bypass the fierce rejection response, and will perhaps escape attack in the human body too. "It is evidence that rejection can be overcome," agrees transplant immunologist Kathryn Wood of the University of Oxford, UK.

Eighty-one days is around the longest that researchers have extended a baboon's life with a pig organ — although baboon-to-baboon transplants are still more successful. With extra work, "the likelihood is that we'll be able to go much further", Sachs predicts.

The team has yet to publish the experiments, which were carried out in collaboration with Immerge BioTherapeutics in Cambridge, Massachusetts. Sachs presented the findings in October this year to the International Xenotransplantation Congress in Glasgow, UK.

Experts say that the genetically modified pigs may be the most promising development on the long road towards animal-to-human transplants, or xenotransplants. They hope that animal organs could one day make up for the massive shortfall in available human organs such as hearts and kidneys.

Sugar-free

The pigs lack a gene called alpha-1,3-galactosyltransferase, or GGTA1, which adds alpha-1,3-galactose sugar molecules to its cells. Monkeys and humans harbour a pool of ready-made antibodies that instantly recognize this sugar, prompting a rapid and violent rejection, sometimes within minutes.

Researchers have made genetically modified pigs for transplants before, but these animals carried extra genes that suppress this immune response, rather than avoiding it altogether. The animals that Sachs' team used are also miniature pigs, so their organs are roughly the same size as human ones.

Another team, led by David Ayares of Revivicor in Blacksburg, Virginia, has also found preliminary evidence that pig organs engineered to lack GGTA1 can bypass rejection. Revivicor is a spin-off company from PPL Therapeutics, whose researchers created the transgenic pigs.

Safety first

There are numerous safety and ethical hurdles to clear before researchers can consider transplanting animal organs into humans

The latest experiments do not give the green light to pig-to-human transplants. Scientists must still overcome other rounds of attack by the immune system, such as the tiny blood clots that killed some of Sachs' baboons.

Sachs' team used other tricks to quell organ rejection in the baboons, including drugs that quieten the immune system. Along with the kidney, the researchers also transplanted pieces of pig thymus, which pump out immune cells that do not attack pig tissues.

There are also numerous safety and ethical hurdles to clear before researchers can consider transplanting organs into humans. One concern is that pig organs could carry unknown viruses. Some people also have ethical objections to the rearing of humanized animals as organ factories.

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