NEWS
NEWS

How the first genetically modified pig liver was transplanted into a patient in a vegetative state

Updated

This is a proof of concept. The goal of the strategy is for these organs to serve as a 'bridge' to support the patient while waiting for a human organ

Miniature pigs of the species used for the transplant.
Miniature pigs of the species used for the transplant.AP

On March 10, 2024, a group of Chinese researchers transplanted a pig liver into a patient who was in a vegetative state for the first time.

Their main objective was to verify the viability of the implant, and for 10 days, with the consent of the hospital and the family, they evaluated the evolution of the organ -genetically modified to prevent rejection-, which showed promising results.

All the details of their work are now published in the journal Nature, in an article that explains the procedure and shows a new milestone on the path to xenotransplant clinical practice.

This news coincides with the recent announcement that the FDA, the agency that regulates the authorization of drugs and medical procedures in the US, has given the green light for the first clinical trial with kidney transplants from pigs.

In recent years, several proof-of-concept tests have been carried out demonstrating that it is possible for kidneys or hearts from pigs whose genome has been modified to eliminate risk genes to survive and function at least for a period in a human body.

Editing six genes to prevent rejection

In this first documented case in scientific literature of a pig liver xenotransplant, the researchers edited several genes present in the pig's genome related to rejection and introduced different transgenes to facilitate compatibility with humans. In total, the resulting organ had six genetic modifications.

After obtaining approval from the hospital's ethics committee and permission from the family, they implanted it into a patient who was in a vegetative state, with no chance of recovery. The patient, who did not have any liver problems, kept their own organ, and the implanted one was placed in another part of the abdomen, as explained in a press conference by Lin Wang from the Fourth Military Medical University in Xian (China), the lead author of the study.

For 10 days, the scientists evaluated the organ's function and if there were signs of rejection, as well as blood flow and immune and inflammatory responses. As they confirmed, the pig liver was able to produce bile and albumin, the blood supply remained stable, and there were no signs of hyperacute rejection, a complication that would occur when introducing an organ from another species into a human without any genetic modification. However, the patient was also treated with immunosuppressants, as is customary in any conventional transplant.

At the family's explicit request, the experiment ended after 10 days.

The results of this proof of concept, as noted by the researchers in the medical journal and detailed by Wang to the press, indicate that this type of xenotransplant could be viable and function in a human body. Nevertheless, the scientists emphasize that their model is not developed to permanently replace a damaged liver but to serve as a 'bridge organ' temporarily while the patient awaits a human liver. "Although the organ was capable of producing pig bile and albumin in this study, it is unlikely that this production would be sufficient to sustain the human body for an extended period," they point out.

A temporary solution: "bridge organs" towards definitive ones

According to Beatriz Domínguez-Gil, director of the National Transplant Organization (ONT), this is "a very good study, well designed and well analyzed, adding to the series of cases of genetically modified pig xenotransplants that have been carried out mainly in the US in recent years."

"It is a step forward in the clinical development of xenotransplantation, although there is still a long way to go," she points out.

The specialist highlights that in this model of auxiliary liver transplant, the basic parameters analyzed regarding graft function as well as hemodynamic, immunological, and inflammatory aspects seem to show, in general terms, that the organ is functioning, leading scientists to deduce that "this auxiliary liver xenotransplant could work in patients with acute liver failure as a way to support that person until they receive the needed transplant or their liver recovers."

It is "a proof of concept that this type of transplant could work, with some caveats still, in that clinical model," she emphasizes.

Rafael Matesanz, creator and founder of the National Transplant Organization, shares the same opinion. In statements to SMC Spain, he mentions that the team behind the advancement, "which has extensive experience" in experimental pig-to-monkey transplants, "was not aiming to achieve a standard liver transplant but rather to serve as a 'bridge organ' in cases of acute liver failure, awaiting a human organ for the definitive transplant. The experience lasted for 10 days, and the pig organ remained in good condition, with an acceptable basic metabolic function and no signs of acute rejection, indicating that the procedure was successful for the intended purposes and could be used in vivo in the near future."

"This is an important experience that opens a different path from what has been tried so far in both vital (heart) and non-vital (kidney) organs, such as the temporary replacement of the diseased liver until a human one is obtained for the definitive transplant," he emphasizes.

First clinical trials with kidneys in the US

The news of this xenotransplant comes shortly after the FDA approved the first clinical trial to evaluate whether genetically modified pig kidneys can be successfully and safely transplanted into humans.

Until now, these interventions had been limited to sporadic, experimental cases authorized for compassionate use. However, the trial, led by the biotechnology company United Therapeutics, is approved to initially assess six patients with end-stage renal disease, with the possibility of expanding it to 50 individuals.

The trial can recruit patients with a high likelihood of dying on dialysis within five years as well as patients without an indication for a conventional transplant, a situation that Domínguez-Gil finds at least "questionable."

"It is hard for me to understand that a patient is not eligible for a human kidney transplant but is for a xenotransplant," she points out.

Nevertheless, this news is a sign of the progressive development towards clinical xenotransplantation, according to the specialist.

"Our goal is to increase the availability of transplantable organs to offer a therapeutic alternative to lifelong dialysis for a large population of patients with limited chances of receiving an allogeneic kidney transplant," stated in a press release by NatureLeigh Peterson, Executive Vice President of Product Development and Xenotransplants at United Therapeutics.

In 2023, there were nearly 90,500 patients in the US waiting for a kidney transplant. Of them, 31% were transplanted the same year. In the European region, which includes 43 countries, the waiting list for kidney transplants consisted of over 108,000 patients, with 25% receiving transplants, and 12 patients dying daily, according to data from the Global Observatory on Donation and Transplantation.

Data from the National Transplant Organization shows that as of December 31, 2024, there were 4,359 adult patients and 29 children in Spain awaiting a kidney transplant. Last year, 4,047 kidney transplants were performed, a 10% increase from the previous year in our country.