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Thousands of patients die every year in the United States waiting for a suitable donor organ. So surgery professor David Sachs has been trying to figure out how to successfully put a pig organ into a primate. The Massachusetts General Hospital researcher and clinician thinks he has almost found the right protocol: a combination of organs from miniaturized, genetically engineered pigs and pig immune tissue that can prime the primate immune system to accept foreign parts.

The longest any animal has survived such a transplant is 83 days, still far short of the one-year survival time that Sachs, director of the Transplantation Biology Research Center at MGH, considers a benchmark to start human trials. But he thinks with a few minor tweaks, the procedure will be ready to try in patients, possibly in as little as five years.

Sachs believes that pig-to-human transplants are the best near-term solution to the drastic shortage of donor organs. As of September 25, 2006, more than 93,000 people in the United States were on the waiting list to receive an transplant organ. Last year, 6,500 people died waiting for such an organ. “People are dying every day for lack of organs,” says Sachs. “Genetic engineering and stem cells promise to cure these diseases–but not in the near term.”

Transplantation between two different species, which is known as xenotransplantation, is not easy. To date, pig skin and pig valves have been used in human transplants, but not entire organs. When patients get an organ transplant from a human donor, doctors stave off immune rejection with organs matched to the recipient’s tissue type and heavy doses of immunosuppressant drugs.

But when organs are transplanted between species, immune attack is swift and much more severe. Pigs and other animals have a specific sugar not present in humans and old-world primates. So when a pig organ is transplanted into a baboon, for example, antibodies circulating in the baboon’s blood immediately swarm and attack the pig tissue, leading to the death of the organ.

Scientists made a major advance in overcoming this immune barrier in 2002 by creating genetically engineered pigs that lack the enzyme that attaches the sugar to the surface of pig cells. In a paper published in Nature Medicine last year, Sachs showed that baboons given kidneys from these genetically modified pigs lived for up to 83 days, far longer than the average 30-day survival time for animals receiving regular pig kidneys.

Sachs’ team also transplanted an additional piece of pig tissue, an immune system organ called the thymus, to prime the baboons for the transplant.

“Engineering the graft itself in ways that might reduce toxicity to the recipient is revolutionary because it potentially makes transplantation much safer,” says Jeffrey Platt, head of the Transplantation Biology Program at the Mayo Clinic in Rochester, MN.

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Tagged: Biomedicine

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