The kidneys filtered blood, produced urine, and were not immediately rejected. A breakthrough.

Researchers have succeeded in transplanting two genetically modified pig kidneys into a brain-dead man. They write that in a magazine American Journal of Transplantation. A major breakthrough, with far-reaching consequences. “Our study suggests that xenotransplantation (the transfer of organs from an animal to humans, ed.) of pig kidneys can be done safely and is feasible,” said researcher Jayme Locke in conversation with Scientias.nl.

Donor shortage

We are currently facing a huge donor shortage worldwide. The waiting list for organs in the Netherlands is also unacceptably long, as a result of which patients die every year while waiting for a donor organ. The largest group of patients waiting for a new organ are kidney patients. As of December 31, 2021, there were 877 people on the waiting list for a new kidney from a deceased donor. “The need for organs extends well beyond the kidney transplant waiting list,” Locke says. To do something about that, scientists have been experimenting with pig organs for some time now. “Xenotransplantation offers hope,” Locke continues. “Not only for those on the waiting list, but also for the others who will never make it to that same waiting list.”

Rejection

Scientists have been trying for some time to find out whether it is possible to modify certain pig organs in such a way that our own body does not reject them. A rather complicated and complex problem. Because transplanting a human organ does not always go smoothly. “The human immune system fights infection by distinguishing ‘foreign’ bacteria and viruses from healthy ‘own’ tissue,” explains Locke. “Another person’s organs look so different that anti-rejection drugs are needed to prevent attacks from one’s own body – also known as rejection. However, pig kidneys look so strange that anti-rejection drugs aren’t even enough. Therefore, certain genetic adjustments are needed to make the pig organ more human-like.”

Humanoid Pig Kidneys

In a new study, researchers took up that challenge. The researchers took pig kidneys that were then genetically modified through ten key gene edits. This made the kidneys more suitable for humans.

Image: University of Alabama at Birmingham

Then the genetically modified pig kidneys were transplanted into a 57-year-old man, who was brain dead. The person in question was kept on a ventilator to keep his body functioning during the study. His own kidneys were removed and replaced with the two genetically modified pig kidneys. “Thanks to this brain-dead man, we were able to test our system without endangering a living person,” Locke said.

The pig kidneys are placed in the human recipient. Image: Jeff Myers, UAB

The operation was successful. In addition, the implanted pig kidneys were found to function well. They filtered blood, produced urine and were not immediately rejected. In fact, the kidneys continued to work until the experiment ended 77 hours after transplantation. “This groundbreaking moment in the history of medicine represents an important milestone in the field of xenotransplantation, which may be the best solution to the current donor shortage,” Locke underlines.

“This groundbreaking moment in the history of medicine represents an important milestone in the field of xenotransplantation”

Safe and feasible

According to the researcher, the findings are promising. “Our study shows that pig-to-human kidney transplantation can be done safely and systematically, helping thousands,” she says. “We were able to properly test our xenotransplantation system. Essentially, we replicated every step in the transplantation process and demonstrated that this is achievable using a pig donor. In addition, we have shown that there was no transmission of diseases and endogenous retroviruses, and that no porcine cells entered the circulation.”

We’re not there yet

Although the study has great potential, we are not there yet. “We still have a lot of things to figure out,” Locke says. “For example, whether pig kidneys are also accepted by the body over a long period of time and otherwise leave the human immune system undamaged. But we expect that pig xenografts can be transplanted successfully and last for the rest of a person’s life, since we know that pigs have a life expectancy of about thirty years. However, the only way we can know for sure is by testing it in living people.”

Approval

It is expected that it will not be very long before xenotransplantation becomes the order of the day. “We think xenotransplantation could be widely available in the next 5-10 years,” said Locke. However, this requires the approval of the competent authorities first. In addition, there are also some ethical objections that need careful consideration. How neat is it, for example, to use an animal as a culture vessel and only bring it into the world, only to rid it of (vital) organs a short time later?

In any case, the current study shows that xenotransplantation is possible. An important breakthrough, which would not have been possible without the human recipient who made his body available for science. Thanks to this 57-year-old man, researchers have been able to answer critical safety questions and make progress towards bringing xenotransplantation one step closer. “His contribution will save thousands of lives and it could start in the very near future,” says Locke. “We have now been able to fill important knowledge gaps and collect data needed to initiate clinical trials in living people with renal failure.”