Hooking Up Human Lungs to Pigs Could Save Them for Transplant
Donated lungs have a short shelf life. After they’re removed from a donor, it’s a race against the clock to get them to a lucky recipient. The delicate, spongy organs are viable for only six to eight hours at most — if they’re suitable for transplant at all.
After a person dies, the lungs are often damaged, inflamed, or filled with fluid. As a result, only about 20% of donated lungs are deemed acceptable for transplant, a lower percentage than other organs, like the kidneys. More than 1,000 people in the United States are currently waiting for a lung transplant. These people may wait months or years to get a new lung.
Researchers at Columbia and Vanderbilt sought to extend that window of viability and buy enough time to reverse the damage using live pigs. By hooking up lungs that had been rejected for transplant to the pigs, the scientists were able to revive the lungs in 24 hours. The new technique could one day expand the number of donor lungs available for transplant, potentially saving more lives. The scientists published their results July 13 in the journal Nature Medicine.
“We were able to repair these lungs and achieve remarkable improvements in their function,” senior author Gordana Vunjak-Novakovic, a professor of biomedical engineering and medicine at Columbia University, tells OneZero.
“This approach is very novel and certainly shows promise,” says James Fildes, a transplantation scientist at the University Hospital of South Manchester in the U.K., who wasn’t involved in the work. “A major logistical challenge of lung transplantation is keeping the preservation time as short as possible, as longer times result in poor function following transplant.” But whether it will be feasible in sick patients awaiting transplants still needs to be determined.
The United States performed 2,562 lung transplants in 2018, a 31% jump over the past five years, according to a federal report. Despite that increase, 365 people died while waiting for a lung transplant or became too sick to undergo the procedure. And the number of people needing a lung transplant could soon grow because of the coronavirus pandemic. The virus is known to ravage the lungs, and in some cases it can cause long-lasting damage. In June, a previously healthy woman in her twenties became the first in the United States to receive a double lung transplant for Covid-19.
“There could potentially be a tsunami of need for lung transplantation in the years to come.”
Currently, a technique called ex vivo lung perfusion can be used to keep donated lungs breathing a few extra hours. Known as a “lung in a box,” the method involves putting the organ into a sterile plastic dome with a pump that feeds it oxygen and nutrients. But not all donor lungs can be rescued with this method.
In the new study, a 25-person team led by Vunjak-Novakovic and Matthew Bacchetta, associate professor of thoracic surgery at Vanderbilt University, wanted to find a more lifelike way to sustain and repair a lung.
“The idea was if we could at least temporarily support these human organs, they would recover from these acute reversible injuries, and then we would be able to utilize them for transplantation,” Bacchetta tells OneZero.
The researchers acquired six donor lungs — five pairs plus a single one — that had been deemed unsuitable for transplant. Placing each lung into a clear plastic box, they connected the box to a ventilator, a machine that aids in breathing. Next, they joined the lungs with the circulatory system of a live pig, which was put under anesthesia. Two tubes connected the major blood vessels in the lungs to the either side of the pig’s neck, allowing the pig’s blood to flow through the lungs and back to the pig. After being connected to the pigs for 24 hours, the damaged lungs began to recover.
Before the procedure, the single lung was so swollen and fluid-filled that it was declined by multiple transplant centers and eventually offered for research. It had been outside of the body for 22 hours and didn’t improve after five hours with the existing lung-in-a-box method. But after being hooked up to the pig, it met transplant criteria.
In a previous study, Bacchetta and Vunjak-Novakovic used this same approach to revive damaged pig lungs that had been removed from the body. They were able support them for as long as four days. They say the technique works by mimicking the body’s natural repair mechanisms. If human lungs could be kept alive that long, it could be a game changer for transplants. Beyond lungs, the researchers think the system could support and repair whole limbs, as well as other organs, such as livers or kidneys.
“We lose a lot of people on the waitlist, and we really would like to be able to open up lung transplant to more people,” Bacchetta says. “If we could increase our recovery rate on organs, it would open up the opportunity for more transplants for people who need them.”
Bacchetta says there are two possible applications for this research. Pigs could be used to recover donor lungs, or patients themselves could be connected to their new lungs before transplantation. The pig approach risks the chance that pig cells lingering in the lungs could spur an immune reaction in patients and cause the body to swiftly reject the transplanted organ, Fildes says. Pigs also carry viruses that could potentially be passed on to people.
Because of these risks, Bacchetta says connecting a transplant patient to a lung could be safer and more practical. Abbas Ardehali, surgical director of the UCLA Heart and Lung Transplant Program, says the technique looks promising, but there will also be challenges with this approach. It’s not known whether lung transplant recipients — who typically have the most severe form of lung disease — would be able to support a donor organ as well as a healthy pig can.
“As you can imagine, a healthy person would never be the recipient of a transplanted organ,” Ardehali says. “Some of these patients are quite ill, and they may not be the most stable to undergo this process.”
Before the technique can be tested for lung transplant patients, the researchers say they will have to study more lungs, and for longer periods of time, to make sure there aren’t any adverse side effects in the pigs or lungs. But if they’re able to perfect the technology, it could eventually expand the supply of available donor organs.
Researchers have already found ways to expand the donor pool. For example, donor lungs that test positive for hepatitis C can now be transplanted in patients thanks to new curative medications, and the recent lung-in-a-box advance is able to preserve and restore some lungs of “marginal” quality.
Meanwhile, scientists are working on more futuristic options, like growing lab-made lungs from stem cells and trying to genetically modify pigs to make their organs more suitable for human transplantation. But these ideas are still far from reality. The cross-circulation system developed by the Columbia and Vanderbilt team isn’t yet ready for routine use, but Ardehali says it warrants further testing. As the Covid-19 pandemic drags on, he says now is the time to consider ways to increase the availability of more donor lungs.
“We don’t know how many of the 3 to 4 million Americans who have been infected with Covid-19 will need an organ transplantation a few years from now,” Ardehali says. “There could potentially be a tsunami of need for lung transplantation in the years to come.”