Pig kidneys frozen for months rewarmed and shown to work after transplant

The kidneys, which are similar in size to human ones, were left in a glass-like state. After rewarming, testing in machines, and transplantation into pigs, they regained their color and produced urine, key signs that they were working, the researchers reported. The work has not yet been peer-reviewed.

Erik Finger, a transplant surgeon at the University of Minnesota who co-led the work, said: “Ten years ago … I wouldn’t say I had high hopes it was actually going to work.” After the last transplant, he said, “I walked out of the room and said, ‘This is a big deal.’”

Outside researchers called the result a milestone. Peter Kilbride, a cryobiologist and cofounder of Kyros Kairos, a company focused on improving funding for cryopreservation research, who was not involved in the work, said: “Thank God that someone’s actually managed to do it in one organ and prove that it works.” He added that people had been trying and failing to reach this step for years. Korkut Uygun, a biomedical engineer and professor of surgery at Harvard Medical School, who was also not involved, said: “Their work is amazing and will enable us to truly, indefinitely bank organs.” He called it “a revolutionary time for transplantation.”

The advance addresses a longstanding limit in transplantation. Tens of thousands of organ transplants take place in the US alone each year, and these procedures are thought to have saved 2 million years of life in the last 25 years, according to the report. But organs can currently be preserved for only 24 to 36 hours, making it difficult to get them to the right recipient in time. Transplant recipients also must take drugs that suppress their immune systems for the rest of their lives; the drugs prevent rejection but carry side effects and increase the risk of infections and cancer.

Long-term organ banking could give doctors more time to match organs to recipients and potentially prepare recipients and their immune systems beforehand, reducing the risk of rejection. Finger said: “With real organ banking … instead of the patients waiting for the organ, it’s the organs that are waiting for the patients.”

The technique builds on vitrification, a process that cools cells to ultra-low temperatures and turns them into something like glass. It is already used to store eggs, sperm, and embryos, but vitrifying whole organs is much harder. Cryoprotectants—chemicals that work like antifreeze—can prevent damaging ice crystals from forming, but they tend to be incredibly toxic. Large tissues are also difficult to cool rapidly and uniformly, and just as hard to rewarm evenly all the way through.

Finger and colleagues, working with John Bischof, a bioengineer at the University of Minnesota, came up with a solution. After loading an organ with a cryoprotectant, they infuse it with iron oxide nanoparticles. The nanoparticles do nothing to the cells, but when it is time to rewarm the organ, they can be activated with an electromagnetic field. When the radiofrequency of that field switches between two states, the particles flip, realigning themselves with the field and releasing heat throughout the organ. Adjusting the power of the field lets the team control the heating rate so that it gets faster once the organ reaches -120 °C.

The researchers successfully vitrified rat kidneys using this approach in work published in 2023. They rewarmed kidneys that had been kept in a freezer for up to 100 days before transplanting them into rats. Since then, the team has tried to achieve the same success with bigger organs. Pig kidneys are thought to be a good model for human ones because they are about the same size and look similar. Rat kidneys weigh around one gram; pig kidneys are around 100 grams. The cryoprotectant used for vitrifying rat kidneys did not work as well in the pig organs. “We had to rediscover and modify the cocktail,” Bischof said. “That’s why it’s taken us three years.”

The procedure begins by removing a kidney from a donor pig. Once it is out, the kidney is flushed with a commonly used organ preservation solution to remove the blood, according to the report. The kidneys are not perfect, and the researchers have yet to demonstrate that they can sustain life over the long term. The findings were shared on bioRxiv and have not yet been peer-reviewed.