Researchers from the National Heart, Lung and Blood Institute (NHLBI) in Bethesda, Maryland, have managed to keep a pig heart beating for 945 days inside the body of a live baboon. This record-breaking outcome leaves scientists hopeful for the potential for xenotransplantation, the transplantation of animal organs or tissues into humans, to address worldwide organ shortages.
A number of animal species have been considered as potential candidates for organ transplantation. Chimpanzees seemed like the obvious option due to the similar size of their organs and good blood type compatibility, but were ruled out as they are an endangered species. Baboons were also considered, but presented their own set of problems, including smaller body size, infrequency of blood type O and long gestation period. This has led to pigs becoming the potential organ donor of choice, as they share multiple complementary proteins with humans and their organs are of a similar size.
But the response from the recipient's immune system has been the source of most problems surrounding xenotransplantation, and the team had a number of early transplant rejections due to protein incompatibility between baboons and pigs. To reach the 945 day milestone and smash the previous record of 179 days, a group of baboons was given a cocktail of immune-suppressing drugs containing a key antibody called anti-CD40, which exhibits the potential to resist attacks by the immune system. The hearts of the genetically modified "gene knockout" pigs were also engineered to lack alpha 1-3 galactosyltransferase, a highly incompatible enzyme that causes blood clots in primates. The scientists said it was this combination that was essential to the success of the experiment.
Over the course of the experiment, the researchers lowered the immunosuppressant dose given to the baboons in hopes they had developed a tolerance to the pig hearts, but found that once the anti-CD40 antibody left their system the baboons died, so a maintenance dose was still required. At this stage, this same maintenance dose would need to be taken regularly by a human recipient, leaving them highly susceptible to other sicknesses.
Currently there is a global shortage of organ donors, with US waiting lists receiving a new patient every 10 minutes and, on average, 22 people dying each day waiting for transplants. The researchers believe that their approach could lead to porcine hearts and other organs being potential candidates for xenotransplantation for thousands of patients requiring transplants.
However, there is still a while to go before we're walking around with beating bacon hearts, with the researchers warning that keeping a heart alive in an abdomen is much easier than getting one to pump in the chest. The abdomen was chosen so as to not kill an unnecessary amount of baboons, and to reduce time spent on surgery. But having achieved some success, the researchers are now planning to perform heart replacement surgeries on another group of baboons.
"People used to think that this was just some wild experiment and it has no implications," Muhammad Mohiuddin, a cardiac transplant surgeon at NHLBI who led the study, tells Science. "I think now we're all learning that [xenotransplantation in humans] can actually happen."
Source: Nature Communications
