Pig kidneys that were “frozen” for a year have been brought back to life
Pig kidneys that were cooled to -150 °C and stored in a freezer for months have been successfully rewarmed and shown to work again for the first time, say scientists. They hope to replicate the findings with human organs. The kidneys—which are similar in size to human ones—were left in a glass-like state, in one case for over a year. Once they had been rewarmed, tested in machines, and transplanted into pigs, the kidneys regained their color and made urine—key signs they were working. “Ten years ago … I wouldn’t say I had high hopes it was actually going to work,” says Erik Finger, a transplant surgeon at the University of Minnesota who co-led the work. “After we did the last transplant, I walked out of the room and said, ‘This is a big deal.’” The research was shared at the preprint server bioRxiv and has not yet been peer-reviewed. The kidneys aren’t perfect, and the researchers have yet to demonstrate that they can sustain life over the long term. But the results represent a milestone achievement, say others in the field. “Thank God that someone’s actually managed to do it in one organ and prove that it works,” says Peter Kilbride, a cryobiologist and cofounder of Kyros Kairos, a company focused on improving funding for cryopreservation research, who was not involved in the research. “For years, people have been trying and failing to get to this step. Finally, we’ve got this breakthrough.” “Their work is amazing and will enable us to truly, indefinitely bank organs,” says Korkut Uygun, a biomedical engineer and professor of surgery at Harvard Medical School, who was also not involved in the research. “It is a revolutionary time for transplantation.” Buying time Every year, tens of thousands of organ transplants take place in the US alone. These procedures are thought to have saved 2 million years of life in the last 25 years. But there’s plenty of room for improvement. One major challenge is the lack of available organs. Even when an organ becomes available, it can be difficult to get it to the right recipient within 24 to 36 hours, which is the current limit for preserving human organs. People who receive organ transplants must also take drugs that suppress their immune systems for the rest of their lives. These drugs are meant to stop their bodies from rejecting the new organs. But they come with side effects and increase the risk of infections and cancer. The ability to bank organs for long periods of time holds the promise to address all these challenges. Doctors would have more time to match organs to recipients. They’d be able to limit the risk of organ rejection, too—potentially by preparing recipients, and their immune systems, beforehand. “With real organ banking … instead of the patients waiting for the organ, it’s the organs that are waiting for the patients,” says Finger. Scientists have been able to cool cells to ultra-low temperatures through a process called vitrification, which essentially turns them to something like glass. This procedure is already used to store eggs, sperm, and embryos. Vitrifying whole organs is much harder. Some problems can be avoided with cryoprotectants—chemicals that work like antifreeze and prevent damaging ice crystals from forming. But these chemicals tend to be incredibly toxic. It’s also difficult to rapidly and uniformly cool large tissues, and just as hard to evenly rewarm an organ all the way through. Working with John Bischof, a bioengineer at the University of Minnesota, Finger and colleagues have come up with a solution. Once an organ has been loaded with a cryoprotectant, they infuse it with iron oxide nanoparticles. These nanoparticles don’t do anything to the cells. But when it’s 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 also flip, realigning themselves with the field. That causes them to release heat throughout the organ. Adjusting the power of the field allows the team to control the rate of heating 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. Back then, they were able to rewarm kidneys that had been kept in a freezer for up to 100 days before transplanting them into rats. Since then, the team has been trying to achieve the same success with bigger organs. Pig kidneys are thought to be a good model for human ones—they’re about the same size and look similar. Rat kidneys weigh around one gram; pig kidneys are around 100. It hasn’t been easy. The cryoprotectant used for vitrifying rat kidneys didn’t work as well in the pig organs. “We had to rediscover and modify the cocktail,” says Bischof. “That’s why it’s taken us three years.” Deep-freezing kidneys The first step in the procedure is to remove a kidney from a donor pig. Once it’s out, the kidney is flushed with a commonly used organ preservation solution to remove the blood, bagged, and temporarily laid on a bed of ice in a cooler so it can be taken over to the engineering lab. There, team members unpack the kidney and hook it up to a device they’ve designed to control the organ’s temperature and pressure. Then they start to load it up with the cocktail of cryoprotectants, slowly enough to ensure an even spread through the organ but quickly enough to minimize any toxic effects. It takes around two hours. The next step is to infuse the organ with the iron oxide nanoparticles, which are pumped through the organ for around seven to eight minutes, says Finger. Then it’s time to cool the organ by pumping cold nitrogen vapor into a chamber housing it. It’s a delicate process, and the team must ensure that the organ is cooling all the way through. At the same time, they must lower the kidney’s temperature as quickly as possible to prevent ice from
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