Pig's blood as a cure may sound mediaeval. But seeding animals with pig blood cells is one strategy for success in pig-to-primate organ transplants. And the complications created may throw light on a common hitch in human-to-human bone-marrow transplants.

Xenotransplantation, such as the transfer of pig organs to humans, holds hope of relieving current shortage of transplant organs. But it triggers an immediate and massive immune-rejection response.

Transplants of the donor's bone-marrow stem cells, which generate blood cells, may prepare the body to tolerate a subsequent organ transplant. Bone marrow produces the white blood cells that attack foreign tissue. Researchers hope that the transplanted cells will replace those that normally recognize and reject donor tissue. The aim is to create a persistent mix of host and donor bone-marrow cells.

"We're trying to [induce] long-term tolerance to the graft," explains Robert Sackstein of Harvard Medical School in Boston, Massachusetts. Testing pig-to-baboon bone-marrow transplants, he and his team reasoned that flooding baboons with pig stem cells should encourage the grafts to settle.

As they increased the number of pig cells, they hit a complication: they detected damage to the baboon's red blood cells caused by blood clots in the lining of their blood vessels¹. "It put a wrench in our gears," he says.

But the setback may have a useful spin-off. The team believe that they have stumbled on an animal model for studying a human condition - thrombotic microangiopathy - in which the clots in blood-vessel linings snag and rip passing red blood cells.

"It's like putting a piece of cheese through a cheese wire," explains Anthony Warrens, who works on xenotransplantation at Hammersmith Hospital in London. The condition, which affects up to 14% of human bone-marrow transplant patients, can cause brain damage, renal failure and even death.

The body fights grafts, but grafts fight back, explains Thomas Starzl, a transplantation pioneer at the University of Pittsburgh, Pennsylvania. The blood clotting that Sackstein found may be a symptom of graft-versus-host disease (GVHD), in which transplanted cells attack their new body.

Bone-marrow transplants are used to treat certain cancers such as leukaemia and lymphomas, replacing cancerous blood cells after chemotherapy. The likelihood of developing GVHD depends on how well-matched donor and host tissues are.

Cross purposes

This research also highlights the kind of hurdles still faced by xenotransplantation. Using bone marrow to get donors to accept grafts is one way to overcome the mutual rejection reaction. "A lot of people are very enthusiastic," says Warrens.

"Sackstein's group deserves a lot of respect for tackling this tough problem," admits Starzl. Like other primates, our reaction to pig tissue is particularly severe: we carry antibodies directed against a molecule on the surface of pig cells. This innate immune response is "merciless," says Starzl, and can destroy alien organs in less than a day.

Starzl's team takes an alternative approach. They are genetically modifying pigs to remove the offending gene. "We're trying to 'humanize' the graft," he says.