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Xenotransplantation

The grafting of cells, tissues, or entire organs from one species to another.

Today, the number of people needing organ transplants far exceeds the supply of human donor organs. Xenotransplantation of organs from animals may someday help close this gap. Diabetes researchers hope, for example, that it will become possible to transplant islets of Langerhans from pigs into people with Type 1 diabetes, whose bodies are unable to make insulin. The islets of Langerhans are the tiny groups of cells in the pancreas that produce insulin, and giving fully functional islets to individuals with Type 1 diabetes might make it possible for them to make their own insulin, virtually curing them. The same result could be achieved by transplanting an entire pancreas, but transplanting just the islets should be simpler, easier, cheaper, and very likely safer.

For decades, researchers have been experimentally transplanting islets of Langerhans from human donor pancreases into people with diabetes, without a great deal of success. In part, this was because some of the immunosuppressive drugs that were used to keep the body from rejecting the transplanted islets were toxic to the islets themselves. In the past few years, there has been remarkable improvement in the success rate of islet transplantation using the Edmonton Protocol, a procedure developed by researchers at the University of Edmonton in Canada that uses newer, safer immunosuppressive drugs, along with other refinements in the transplantation process.

More than 80% of people treated with this protocol have been able to stay off insulin for at least one year following transplantation, so researchers are now confident that islet transplantation can work. Nonetheless, because of the potentially toxic immunosuppressive drugs required, islet transplantation is reserved only for people with severe blood glucose control problems or for people also receiving a kidney transplant, who require immunosuppressive drugs anyway.

Another major impediment to widespread use of islet transplantation is the scarcity of donor islets. The available pancreases from human donors in the United States would provide enough islets for only about 1/10 of 1% of the people who could benefit from them. Clearly, if islet transplantation is to become widely available, other sources of islets must be found — and pigs may some day serve as one such source.

Researchers think pigs might make good organ donors because their organs are of roughly human size — unlike the organs of, say, chimpanzees, which are genetically closer to humans. Heart valves from pigs have been used in humans for decades. Scientists are exploring the possibility of transplanting pig hearts, livers, kidneys, and pancreatic islets into humans. Pigs exist in large numbers and in theory could provide a virtually unlimited supply of whole donor organs and islets for transplantation.

Ordinarily, whole organ xenografts from pigs provoke hyperacute rejection, in which the human immune system quickly attacks, cutting off the blood supply and causing the organ to fail, often within minutes. Researchers have discovered that this attack targets a certain molecule on the surface of pig cells — a sugar called alpha-1,3-galactose (or “Gal”). In late 2001 and 2002, researchers made a major step forward in whole organ xenotransplantation by cloning pigs that lack the gene responsible for the appearance of the “Gal” molecule on their cells. Such pigs might some day serve as ideal organ donors for humans.

According to some transplant researchers, pig islets may be easier to transplant into humans than whole organs because they don’t have much, if any, “Gal.” In fact, in the early 1990’s, doctors at Sweden’s Karolinska Institute transplanted fetal pig islets into 10 people with Type 1 diabetes, using standard immunosuppression, and some of these islets survived for up to a year. The Swedish researchers believe that xenotransplantation of islets requires different immunosuppressants than human islet transplantation, and that a different immunosuppressive regimen could be developed that would work specifically for islet xenografts.

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