In demand donor (Image: Johner Images/Getty)

The unprecedented survival of pig hearts in four baboons for almost 600 days has revived hopes that animal organs could help alleviate the global shortage of organs for transplant.

Huge strides have been made in recent years creating and successfully transplanting human organs using stem cell technology. Despite this, the potential for using animal organs in humans – xenotransplantation – remains attractive because the supply is theoretically limitless, and could supply organs of any size.

However, the technology has taken decades to get off the ground, because of safety fears and problems with organ rejection.


“We’re confident we’ve tackled most of the immunological barriers, and although it would be very premature to speculate on a timeline to the first transplant in humans, I would say we are much closer to clinical reality,” says Muhammad Mohiuddin of the US National Heart, Lung and Blood Institute in Bethesda, Maryland, who lead the latest baboon trial.

Designer piglets

Until now, pig hearts have survived for up to six months in monkeys, so the latest results treble the survival time. The piglets from which the hearts were taken were genetically engineered to disguise their hearts from the baboons’ immune systems and to prevent blood clots from forming in the organ.

Four genetic tweaks were made. The first eliminated the gene that makes alpha 1,3 galactosyltransferase. This enzyme makes a carbohydrate on the surface of pig cells that gets recognised and attacked by the immune system of the other animal. Knocking out the gene effectively makes the pig organs immunologically invisible.

The second alteration is an added gene, called hCD46, which produces a protein that prevents the baboon – or theoretically, human – immune system from attacking the organ. Another added gene, called THBD, makes a human anti-clotting substance called thrombomodulin, may be the most crucial improvement.

“That may be the key here, as the major problem for organs has been [blood clots]. The problem is most dramatic in kidneys but also problematic in hearts,” says Anthony d’Apice, an honorary professor at the University of Melbourne in Australia and a global authority on xenotransplantation.

Another change is adding an antibody drug to the cocktail of immunosuppressant drugs given to the baboon after transplant. The antibody blocks the CD40 receptor on immune cells. “This could be a critical drug,” says d’Apice.

Beating abdomen

Because the experiments were designed to check for rejection rather than function, the hearts were plumbed into blood vessels in the baboons’ abdomens, enabling the baboons to rely on their native hearts to circulate their blood.

Mohiuddin says that the triple gene change plus the upgraded immunosuppression regime should work with other organs, but additional gene tweaks may sometimes be needed. The regime is also likely to need to be tweaked before the organs could be transplanted into humans, but the basics would be the same.

“The key to success is a combination of transplantation skill, the use of the right genetics and immunosuppresion,” says Mohiuddin, who presented the results at the annual meeting of the American Association for Thoracic Surgery in Toronto, Canada, this week.

Now the immunotherapy step has been solved, Mohiuddin’s next move is to see if the pig organs work as a replacement for the baboons’ natural hearts.