A first step towards animal transplantation

Is transplanting a pig’s heart ethical?

In Switzerland in 2021, 1,434 people were waiting to receive an organ, 72 of whom died while waiting. Some people sometimes wait several years before a transplant. If animals like pigs could supply the missing organs, would it be ethical to harvest them? For Leo Bühler, professor of surgery at the Cantonal Hospital and the University of Freiburg and a specialist in xenotransplantation, the answer is positive. “We eat meat and the animals are already used in the clinic, mainly for heart vessels and valves.” Another argument in favor of this therapy is that it would reduce international organ trafficking and the exploitation of poor donors, a consequence of global shortages.

In January, a pig’s heart was transplanted for the first time into a patient with heart disease. He survived two months. The use of organs, tissues or cells of animal origin in humans, or xenotransplantation, began about a hundred years ago with the objective of filling the shortage of organs available for transplants. Today, that approach has taken a decisive turn. How was this new type of transplant possible? Will it soon be common? Analysis with two experts.

The pig, close and different from us

During the research, the scientists tested organ xenografts from different animals, such as baboons or sheep. But the pig is the most suitable donor, as Franz Immer, a specialist in cardiac surgery and director of Swisstransplant, explains: “His heart is very similar to ours. It’s the same weight, the same size, and it works in a similar way. Therefore, it is technically easy to transplant into humans.”

But once this heart is in place, the question of rejection arises, as for a human heart transplant. In fact, our immune system recognizes the presence of antigens other than our own on the surface of foreign cells and immediately attacks them to destroy them. To prevent this rejection, recipients are given immunosuppressants. But in the case of an animal organ, the antigens are so different that this treatment is not enough. That is why the pig has been genetically modified so that, on the one hand, it no longer produces antigens capable of triggering rejection and, on the other hand, it expresses human genes that block part of the immune reaction. These modifications are facilitated by the very short generation time of the pig compared to other animals closer to us: they reach sexual maturity in less than a year and give birth to about ten offspring per litter, while a monkey takes ten years to reproduce and give birth to one or two puppies.

In addition to the risk of rejection of the heart, there is another important risk: that of infection of the recipient by swine virus. To minimize this, the pigs are raised in sterile conditions for two generations.

A first step towards xenotransplantation

During the research, the modified pig heart was first transplanted into monkeys, which survived for three years. In the human transplant patient in January, “the heart functioned very well for several weeks with no signs of rejection,” according to a statement from the University of Maryland Medical Center in the United States. The causes of death are currently unknown, but the patient was not an ideal recipient as his condition was critical at the outset. For Leo Bühler, professor of surgery at the Cantonal Hospital and the University of Freiburg and a specialist in xenografts, “it is, however, a great step that has been taken in the field of xenografts. But before this approach becomes clinical routine, the experiment will have to be repeated several times, in highly specialized centers, which will likely take many years.”

In addition to the heart, other organs could be transplanted, such as the kidneys. This is the organ that needs it most: more than 70% of people waiting for a transplant are for the kidney. Late last year, a team successfully implanted pig kidneys into a brain-dead patient to test the technique. However, the pig kidney does not secrete erythropoietin (EPO), the hormone responsible for the production of red blood cells. The recipient, therefore, needs to receive it for life. For more complex organs, transplantation remains unlikely at the moment, according to Franz Immer: “The liver or pancreas, for example, produce many human-specific metabolic reactions that pigs cannot replace. In the case of the heart, the operation is simpler, we can see it as a pump.

Another great challenge is in the production of organs from swine. “The logistics are very complex, as obtaining enough organs would require large breeding centers that meet impeccable sterility standards,” explains Leo Bühler. For the time being, it is still not possible to guarantee the safety of organs in terms of infection and risk of transmission to humans. For the specialist, “it will take at least 5 to 10 years for xenotransplantation to materialize clinically. But we’ve been talking about that deadline for many years,” he said.

to other tracks

Some therapies are now as advanced as whole organ xenografts. “This is the case with the artificial heart (or ventricular assist), which is increasingly implanted after the age of 60, instead of a heart transplant or while waiting for it”, explains Franz Immer, a physician specializing in cardiac surgery and director of Swisstransplant. This small pump placed in the left ventricle collects blood from the lungs to bring it into the aorta. Stem cells and cultured tissues of human origin are also a promising path, according to Leo Bühler, professor of surgery at the Cantonal Hospital and at the University of Freiburg and a specialist in xenotransplantation: “A clinical phase has begun with diabetics receiving stem cells modified to produce insulin.” Xenotransplantation research is also supported at the Swiss level, where scientists have worked on isolating pig liver and pancreas cells. Once coated in a biogel, they are transfused to treat acute liver failure or diabetes. After testing in mammals, human clinical trials are now planned.

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Published in Le Matin Dimanche on 04/17/2022.

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