New stage in the investigation of transplants of transgenic pig organs

Madrid.- Tim Andrew lived for nine months with a genetically modified pig kidney, until it had to be removed, the first non-human liver transplanted to a person was also from that animal, although he ended up dying. Research in xenotransplantation has begun a new stage led by the United States and China.

The lack of human organs has led science to wonder if those from pigs would be viable. Research that has taken important steps, especially in the last year, when the U.S. also authorized the first clinical trials, but which has a long way to go. The new impetus began about four years ago, especially thanks to the CRISPR gene editing technique, which allows modifications to be made in pigs "with ease, compared to what it was before," says Rafael Matesanz, founder of the National Transplant Organization (ONT) to EFE.

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In 2021, xenotransplants of genetically modified pig kidneys began in brain-dead people, and in 2022, the first one was performed on a living recipient; it was a heart transplant, and the patient died two months later.

During the recently ended year, "very important steps have been taken towards achieving the great panacea: organs from pigs that actually work for transplants," he adds.

Last year, the first liver transplant was performed on a living person, the lung transplant on a person with brain death, or the record set by Andrew, until his kidney had to be removed due to rejection, compared to the four months that Towana Looney, also an American woman, maintained it.

Clinical Trials

This last one was performed in 2024 by a team from Langone Health hospital, at New York University, led by Robert Montgomery, who highlights to EFE that the U.S. Food and Drug Administration (FDA) also authorized, in 2025, the first clinical trials with kidneys. The time from the first xenotransplant of a genetically edited pig kidney to a person with brain death, which was done at NYU Langone in 2021, to the first enrollment of a patient in a clinical trial "has been extremely fast". This authorization is, it says, what was needed for "xenotransplantation to become the mainstream treatment for chronic kidney disease."

The trials for final approval "will take a few years to complete and, if the results demonstrate safety and efficacy, xenotransplantation (of the kidney) will be generalized immediately." The FDA also authorized in 2025 another trial, which has not yet begun, for liver xenotransplantation, not as a definitive therapy, but as a bridge until a human one is achieved, adds Matesanz. Clinical trials "change everything", because it goes from a use for very specific cases to something structured. Data will be compared to see if survivals are reasonable and "it will take, at least, a couple of years to assess if it is worth continuing".

A Technological Career

Both the first xenotransplant of a genetically modified pig liver to a living person, and that of a lung to a person in brain death, which remained stable and functional during the nine days of follow-up, were performed by Chinese researchers. The United States and China are leading the latest advances in this field, and Matesanz believes that "at the moment, there is, so to speak, a technological race" between the two. «The difficult thing - he specifies - is not to place the organ, but to generate the animals with the appropriate genetic mutations» to avoid rejection and diseases. Rejection is, by far, the biggest obstacle and «it's about finding the genetic puzzle so that this organ is tolerated».

In the United States, there are companies like Revivicor (United Therapeutics) and eGenesis, and in China, at least two others, dedicated to creating transgenic pigs, which have from more than 60 mutations to only three, he adds. It remains to be seen "who comes up with the perfect formula", to figure out which molecules to suppress and add, and, when achieved, almost all companies will adopt a similar one.

The Battle for the Kidney

So far, major advances have been made in kidney xenotransplantation, an organ that has shown it is capable "of performing all fundamental functions for long periods of time," highlights Montgomery. Furthermore, it is the organ that undergoes, "by far," the most transplants between humans, "so having another source of kidneys will have a huge impact." Matesanz says that "where the great battle is being fought is in the kidney", an organ for which "global demands are enormous and where companies, which after all are private, seek to make the multi-million dollar investments they have made profitable". But the "big issue" is survival. With a xenotransplant it is now a matter of months, however, with a living human kidney the average survival of the organ is 19 years and from a cadaver 11.7, taking into account that it can be repeated, and on dialysis from five to ten years.

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Open Questions

Xenotransplants have, "from an ethical point of view, many facets" and Matesanz considers that survival is fundamental, especially with the kidney, which is not a vital organ given the other current options. If xenotransplants work, both sources would have to coexist for a time or indefinitely, which raises questions such as who will decide who will have an animal or human organ; would there be first and second class organs? Would it be by order of arrival on the list, by clinical characteristics?. That -he says- would give rise to changes in the distribution criteria. It is also unknown whether the manufacture of organs will have any impact on donation. In addition, it would have legal implications, as those kidneys would, according to current legislation, have the same considerations as a medication, as they are not a human organ. Matesanz points out that the new developments in xenotransplantation are "undoubtedly a spectacular advance, or will be, but they pose a series of new circumstances that will have to be addressed."