Researchers from Columbia University and Vanderbilt University used pigs to repair damaged, human lungs to the point that they could be viable for transplant, according to a study published Monday in Nature Medicine—highlighting a process that potentially could increase the number of lungs available for patients in need.
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'You cannot make a lung in the lab'
Unlike some other organs, lungs are extremely sensitive to damage. Once injured, lungs can fill with fluid and break down, causing leaks in the airways. And because lungs are so fragile, only about 20% of donated lungs can be used for transplant, the New York Times reports.
To address that problem, Gordana Vunjak-Novakovic, director of Columbia University's laboratory for stem cells and tissue engineering, and a group of researchers set out to find a way to increase the number of lungs that are available for transplant.
Originally, the group tried to bioengineer new lungs, but those lungs were too "leaky," Vunjak-Novakovic said. "This was telling us that, unlike other tissues, you cannot make a lung in the lab."
Eventually, a separate group of researchers from the University of Toronto found that pumping nutrient-filled fluid into damaged lungs and attaching them to a ventilator could potentially restore them. However, although the group had used the method to successfully restore and transplant 600 lungs, they found that the process worked for relatively few lungs, the Times reports.
In addition, the lungs could survive being placed on a ventilator under the researchers' method for only a few hours, which limited the amount of damage that could be repaired.
"If you have more time, you have more time to repair the injuries," said Marcelo Cypel, a lung transplant surgeon at the University of Toronto. "You can't reverse a pneumonia in just four or six hours. But if you keep the lung for a few days, you can."
The lungs needed a body
Vunjak-Novakovic and other researchers at Columbia University, along with researchers from Vanderbilt University, then decided to test an advanced version of the method used by the scientists at the University of Toronto. The researchers hypothesized that, to allow damaged lungs enough time to significantly recover, the lungs might need both a ventilator and a body that could remove metabolic waste.
The researchers tested their theory using six damaged lungs that were donated from patients who had experienced brain death. According to STAT News, all the lungs underwent six hours of standard profusion intended to repair and preserve them for transplant, but they'd still been deemed too damaged and denied.
For their experiment, the researchers placed each lung in a plastic box attached to a respirator, which helped the lungs to breathe. Then, the researchers connected each lung to a large neck vein on a live pig, which allowed the pigs' blood to flow through the lungs' vessels. The researchers had infused the pigs with immune suppression drugs to stave off rejection of the human lungs.
Matthew Bacchetta, a lung transplant surgeon at Vanderbilt and a lead author of the new study, explained, "All of a sudden, [the lungs are] attached to a functioning liver, a functioning gut. We don't have to worry about glucose regulation because there's a pancreas. All of these metabolites that are formed are now cleared."
According to the researchers, in just under 24 hours, the lungs looked healthy. Lab tests later confirmed that the damaged lungs had been resuscitated, with many testing at levels typically seen in patients with transplanted lungs. The researchers even found that one lung had been repaired enough to be viable for transplant, though a transplant did not occur.
"The pig was able to keep the lung alive and allow it to repair itself," Bacchetta said.
Procedure could increase access to donor lungs in post-Covid era
The researchers next want to carry out the same experiment with humans, rather than pigs, by connecting the damaged lungs to a patient's neck via a catheter. The process, if successful, would allow a transplant patient waiting for a viable donor lung to resuscitate a damaged lung for their own use, even if they are seriously ill.
"In these patients, their liver works, their gut works, their heart works. But their lungs don't work. So how about if I attach some lungs that are damaged? It's reversible damage. Let their body work essentially as a bioreactor and allow those lungs to heal," Bacchetta explained.
Health experts say that, if the method proves to be effective in humans, it could help to make more lungs available for transplant, especially considering that the global coronavirus pandemic could lead to a greater percentage of donors having lung damage.
"If we could expand the donor pool, we could avoid a lot of waiting-list deaths and could be more open-minded about who could have a transplant," Bacchetta said.
Robert Bartlett—a surgeon known for developing the extracorporeal membrane oxygenation, or ECMO, machine to preserve and treat hearts and lungs—said "many things would change in transplantation" if the new method proves successful. "You could have perfect matching. You could treat organs injured outside the body until they're working well," he said.
Bartlett, who has retired from clinical practice and now leads a lab at the University of Michigan, added that it could be a while before the procedure is proven ready for widespread use, but additional research could help to improve the method's chances of success. "Once we know why it works, we'll really be able to isolate those molecules and achieve the same thing. From work in our laboratory and others, we think that this will be possible within a couple of years."
Zachary Kon, surgical director of the lung transplant center at New York University's Langone Medical Center, said he would "[a]bsolutely" consider using the procedure if it's shown to be safe and effective. "It's a transformative idea that would allow a jump forward in the field," Kon said.
Similarly, David Roe, a lung transplant surgeon at Indiana University, said while the new method seems as if it's "all on the outer cusp," he doesn't "think it is out of the realm of possibility."
"It all makes sense," he said (Kolata, New York Times, 7/13; Cooney, STAT News, 7/13).