Pig-to-Monkey Transplant Treats Diabetes

Embryonic tissue could let xenotransplants evade the host's immune system.

No rejection: Fluorescent red markers show that blood vessels in a transplanted pancreas are of monkey origin. Limited green coloring suggests that few pig blood vessels are present. Credit: PNAS

Using embryonic tissue for interspecies organ transplants offers a way to evade the host's immune system, say scientists who used the method to treat type 1 diabetes in primates. By transplanting embryonic pancreatic tissue from pigs to monkeys, Israeli researchers report that they were able to reverse the primates' insulin deficiency.

The key, the researchers say, is the embryonic tissue's ability to grow into a new pancreas that uses blood vessels from the host animal. The host blood vessels are not subject to the dangerous immune reaction that has always dogged xenotransplants of mature pancreatic material.

The research team, led by Yair Reisner of the Weizmann Institute, claims that the results, published in the latest issue of the journal PNAS, could offer an attractive replacement therapy for type 1 diabetes, an autoimmune disease in which the destruction of the pancreas means that sufferers rely on injections of the hormone insulin to control their blood-sugar levels.

In an earlier study, the researchers found evidence that semiformed pancreatic tissue taken from pig embryos at 42 days of gestation appeared to offer the best combination of characteristics for xenotransplantation. According to Reisner, if they're harvested too early, there may not be enough partially differentiated pancreatic cells. But if taken too late, the tissues' ability to grow into a new organ is diminished, perhaps because they contain too few stem cells, while their ability to cause immune rejection increases.

In the latest study, the researchers transplanted 42-day-old pig pancreatic tissue into monkeys with induced type 1 diabetes. The first pair of animals involved in the study died soon after transplantation from an infection caused by too much immunosuppressive therapy.

The second pair of animals received milder immunotherapy and survived for a year. Furthermore, within five months of treatment, the animals had grown new pancreases and were no longer reliant on insulin injections. This indicates that the replacement organs had sufficient islets--tiny, insulin-producing structures consisting of around 1,500 beta cells, which have their own intricate vascular systems.

Radioimmunoassay tests confirmed that the insulin produced by the monkey was porcine, while the network of vessels running through the new organ was made of host cells. "This is important because it meant the monkey's immune system did not attack the vessels," says Reisner.
This type of immune reaction has been a bugbear for researchers, he says, because primates, including humans, produce a class of antibodies that attack the sugar molecules that coat pig blood-vessel tissue.