When it comes to organ donation, time is everything. As soon as an organ has been carefully removed from a donor’s body, it starts to deteriorate. Surgeons have a matter of hours to get it into a recipient. Leave it too long and the organ will become unusable.
In most cases, organs will be kept on ice during that time, at around 4 °C (39 °F). They cannot be frozen—in previous attempts, ice has formed, causing all kinds of damage.
Matthew Powell Palm at Texas A&M University and his colleagues have an alternative solution—a device that allows organs to be cooled to -4 °C (25 °F) without forming any ice.
Now, in new research with pig organs, his team has shown that kidneys, at least, can be supercooled and preserved in the device for days. Once rewarmed, the organs have been successfully transplanted into animals, and they seem to do better than organs kept on ice.
The work represents “a landmark achievement,” says Kevin Myer, president and CEO of LifeGift, an organ procurement organization based in Texas, who was not involved in the research.
Cooling organs
Powell Palm hopes this approach could ultimately help ease the organ shortage crisis. Today, there are more than 104,000 people waiting for a kidney transplant in the US alone. It is estimated that 17 people die every day in the US while waiting for a transplant. That’s partly due to a lack of donated kidneys, but it’s also because many of those that are available never make it to a recipient. In some years, around one in three donated kidneys end up being discarded, often because they end up too degraded to use by the time they reach a recipient. Kidneys can be stored on ice for around 24 hours or placed in devices that aim to mimic the conditions of the body, also for up to around 24 hours. That’s not always long enough to find a suitable recipient and transport the organ, says Myer.
Scientists around the world have been working on ways to store organs for longer by cooling them to even chillier temperatures. Cooling an organ slows its metabolism—the colder you go, the greater the effect, and the longer you can store it.
We’ve long been able to successfully cryopreserve eggs, sperm, and embryos, but it’s much harder to freeze large organs. Teams have been exploring various temperatures and cryoprotectants (chemicals that essentially work like antifreeze), but so far no one has been able to freeze human organs for transplantation.
As a thermodynamicist, Powell Palm explored another approach. By keeping an organ submerged at a constant pressure, it should be possible to prevent the formation of ice at temperatures a little below 0 °C, without the need for cryoprotectants (which might have side effects and would need to be approved before being used in human transplants).
To test this theory, Powell Palm and his colleagues have created a device that does just that. The device itself is essentially a hermetically sealed chamber with a transparent lid. At its base is a device that monitors the organ’s temperature and checks for the formation of ice. Organs are submerged in a solution that is already commonly used to preserve them for transplant. “I always describe this as low-tech high science,” says Powell Palm. “A lot of work has gone into understanding the … kinetics at play in this system, but ultimately … it’s quite simple.”
Supercooled kidneys
To test their device, Powell Palm and his colleagues first removed single kidneys from pigs. The organs were flushed with the same commonly used solution to remove the blood, just as transplant organs are. The team then kept some kidneys on ice for either two hours or 24 hours, to mimic standard conditions used in human transplantation. They also put some of the removed kidneys in their device for 24, 48, or 72 hours.
The stored kidneys were then each transplanted back into the original donor pigs. Each pig’s second kidney was removed in the same procedure, leaving each animal with only the kidney that had been stored, and reimplanted.
Once the 24-hour supercooled kidneys were transplanted, they immediately began producing urine—a key indication that they were working. The team members also measured other markers of kidney function and found that the organs appeared to be working normally within about 10 days of being transplanted.
That’s slower than kidneys stored on ice for two hours but much quicker than kidneys kept on ice for 24 hours, says Powell Palm.
The organs that were kept supercooled for 48 and 72 hours performed similarly, he says. “Even at three days—triple the clinical standard—we’re getting recovery that is faster than … [what has been] the gold standard for the last three decades,” he says. “So we’re really, really pumped about this.”
“It is impressive,” says Heidi Yeh, a transplant surgeon at Mass General Brigham for Children, who also researches organ preservation technologies. “Often kidneys that have been stored for 48 hours [in other studies] take a week or two before they start working again.”
Organs that grow
The supercooled organs seem to work well in the long term, too. Over a 30-day period, the pigs grew by around 30%—and the kidneys grew with them, almost doubling in size to compensate for both the pigs’ growth and the lack of a second kidney. The team monitored one of the pigs for 200 days before removing and analyzing its kidney. Even at that point the organ looked healthy, says Powell Palm. He and his colleagues presented the findings at the American Transplant Congress in Boston last month.
Earlier this year, researchers in Canada showed they could also cool pig kidneys to below-zero temperatures and transplant them into pigs. The team’s protocol included the use of a cryoprotectant, and organs were stored for up to 48 hours before being transplanted into pigs. Those organs survived for a week.
In supercooling organs for 72 hours and showing that they do well for 30 days or more, Powell Palm and his colleagues have broken new ground. “It’s the first time this has ever been reported in history,” he says.
Those extra hours could make all the difference, says Myer of LifeGift. The advance could give doctors more time to evaluate the kidneys, match them to the most suitable donors, and physically get the organs to their intended recipients in time. It could enable international donations and open up cheaper transport options, he adds. “Right now, with kidney transplantation the assumed limit is 18 to 24 hours,” he says. “If we can get up to 72 hours … that would change everything.”
Powell Palm and his colleagues think they may even be able to go beyond 72 hours. In preliminary studies, organs that had been stored for up to 120 hours appeared healthy, although those organs have not yet been transplanted.
And because the process doesn’t require any cryoprotective chemicals, the team members are hoping for an accelerated approval from the US Food and Drug Administration, which would allow them to test the device in human transplantations.
The storage device is simple and compact, so Powell Palm thinks it will be easy to transport. It hasn’t been tested for air travel yet, but it has been used to take supercooled kidneys across the US in the back of a Kia Sorento, he says: “From a stability perspective, we view this as an even higher bar.”
Powell Palm and his colleague Sebastian Giwa plan to launch a company dedicated to developing the technology, along with other protocols that “stop biological time,” in the coming months, he says.
