By Jessica Hamzelou
SEBASTIAN KAULITZKI / SCIENCE PHOTO LIBRARY
Donated lungs that are too damaged to be used in transplants have been revived after being connected to the blood supply of a live pig. The technique could potentially triple the number of lungs available for transplant, say the researchers behind the work.
As soon as someone dies, their lungs begin to deteriorate. If the person has chosen to donate their lungs, the race is on to get the organs to a recipient as soon as possible. “The lung is very delicate,” says James Fildes at the University of Manchester, UK, who wasn’t involved in the work. “It is one of the most difficult organs to preserve.”
Most donated lungs are only outside the body for a matter of hours. But even then, the majority will have deteriorated so much that they cannot safely be used for transplantation. Only around 28 per cent of donated lungs meet the criteria for transplantation in the US, according to the American Lung Association.
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Doctors can attempt to “recondition” damaged lungs using ex vivo lung perfusion (EVLP) devices that pump oxygenated air and fluid through the lungs, but even then, many fail, says Gordana Vunjak-Novakovic at Columbia University in New York.
Vunjak-Novakovic and her colleagues wondered whether the lungs might do better if they were connected to a living body, with other working organs able to deliver nutrients and remove harmful substances.
To find out, the team obtained lungs that had been rejected for transplantation from six human donors, both single lungs and pairs. One lung had failed even after 5 hours on an EVLP device, and had been outside the body for around 24 hours before the team received it.
The team connected each lung to the circulatory system of an anaesthetised pig for 24 hours, with tubes feeding the blood vessels of the human lung from those in the neck of the pig. At the same time, the lung was pumped with air using a ventilator. Immunosuppressant drugs, which prevent “foreign” tissues from being rejected by the immune system, were added to the circulatory system, infiltrating both the pig and the human lung.
Vunjak-Novakovic’s previous research has shown that the procedure doesn’t seem to cause any lasting effects to the pigs. In one previous experiment, the pigs were able to move around, play with toys and feed while connected to a device used to support lungs taken from other pigs, she says.
Before the treatment, all the lungs had a lot of white areas, suggesting tissue was dying, and weren’t considered capable of getting enough oxygen into the blood.
But after 24 hours of being connected to the pigs, the lungs look transformed. Vunjak-Novakovic and her colleagues performed a range of tests on the lungs, and found that the cells, tissue structure and capacity to deliver oxygen had significantly improved.
Even the lung that had been outside the body for almost two days appeared to have recovered. “That’s remarkable,” says Fildes. “My expectation would be that that lung would be destroyed, but actually it doesn’t look like it is at all.”
“They aren’t 100 per cent normal, but they’re close enough,” says Vunjak-Novakovic. In theory, the lungs looked healthy enough to be considered acceptable for transplant, but she wants to repeat the experiment with many more lungs before implanting treated lungs in people.
Vunjak-Novakovic also plans to use medical-grade pigs, which researchers can be sure won’t harbour potentially harmful pathogens that could be transmitted to people. That doesn’t necessarily mean the lungs will be entirely free of pig cells, however. The lungs in the current study were found to contain white blood cells from the pigs – cells that could trigger an immune reaction in a lung recipient, cautions Fildes.
Eventually, Vunjak-Novakovic hopes that a potential lung recipient could use their own blood supply to revive donated lungs that they will receive. It is unlikely that the approach will rescue the most severely damaged lungs, but “if you can salvage two out of every four that are rejected, you can increase the number of lungs available to patients by three times”, she says.
Journal reference: Nature Medicine, DOI: 10.1038/s41591-020-0971-8
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