The lungs damaged by a deceased donor are often too damaged to be transplanted into someone who needs the life-saving organ.
But scientists have found a way to improve the condition of the lungs that are considered too battered to be of any use.
A host of scientists from Columbia University and Vanderbilt channeled their inner Frankenstein and connected the human lungs to a sedated pig.
The blood from the pigs’ beating heart was channeled into the ventilator-operated lungs, and then the blood returned to the pig.
The experiment used five pairs of human donor lungs, which were classified as unsuitable for transplantation, and each was connected to a live pig for 24 hours.
The research found that each set of lungs was in considerably better condition after a day of “xenogeneic cross circulation.”
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Scientists have found a way to improve the condition of the lungs that are considered too battered to be used for transplants. The damaged human lungs (left) were connected to a live pig and after 24 hours of ‘cross circulation, the condition of the organ improved dramatically (right)
In the image, the experiment is underway. Human lungs can be seen in a protective case and connected to a ventilator and connected to the circulatory system of an anesthetized pig, shown under a sheet on the right side of the image.) Multiple monitors track the progress of the experiment, including thermal imaging, live video, and perfusion statistics – the passage of fluid through the circulatory system to the lungs.
Respiratory disease is the third leading cause of death worldwide, and often the only permanent solution is a complete lung transplant.
However, the lack of donors and adequate organs that are affected by serious but potentially reversible injuries means that many die while on the waiting list.
Scientists have long sought a way to increase the percentage of lungs that perform the cut and can be used in a transplant from the current level of one in five.
One method is called ex vivo pulmonary perfusion (EVLP), which is a six to eight hour process and can recover organs of marginal quality.
“EVLP has undoubtedly changed the rules of the game for lung transplantation, but it remains limited in its ability to resuscitate severely injured lungs,” said Dr. Matthew Bacchetta, co-author of the Vanderbilt University study.
But it cannot make significant progress in repairing severely damaged lungs that require much longer courses of treatment to be viable.
The researchers last year successfully took a pair of pig lungs and connected them to the circulatory system of an anesthetized pig.
Then they discovered that the lungs could be reconditioned with the cross circulation method and began to investigate whether a porcine host could do the same with human lungs.
Five sets of human lungs deemed too poor for human transplantation were connected to a live pig. The pigs’ heart and a ventilator allowed the lungs to function properly for 24 hours and to recover naturally. The method could be used to increase the number of lungs available for transplantation.
Academics say there are two possible ways that research could determine the number of lungs available for transplantation. One would see that critically ill patients already awaiting transplantation with artificial lung support could serve as a cross-circulation host, taking the role of the pig (pictured, a diagram of that potential scenario)
Five damaged lungs, each rejected for transplantation, were donated to the study. One of the organs previously underwent EVLP but did not perform the cut.
The pigs were treated with immunosuppressive drugs to prevent rejection of the lungs and, after 24 hours of connection, the damaged human lungs had improved.
Careful analysis over the course of the single-day procedure saw substantial improvements in tissue quality, inflammatory responses, and respiratory function.
The researchers hope that the method can be used to recover more human lungs from donors and increase the number of organs available for transplantation, which could save thousands of lives.
“We were able to recover a donated lung that was not recovered in the ex vivo pulmonary perfusion clinical system, which is the current standard of care,” said co-author Professor Gordana Vunjak-Novakovic.
“This was the most rigorous validation of our cross-circulation platform to date, showing great promise for its clinical utility.”
Dr. Bacchetta adds: ‘We knew this was our reference study, a human lung that failed in cutting-edge EVLP treatment.
‘If we could make this work on our system then we would be on the right track. It was an eureka moment for our team. ‘
The only lung that failed EVLP was rejected for transplantation due to persistent inflammation and fluid buildup that could not be resolved.
He was rejected for transplantation by multiple transplant centers in the US and was eventually offered for research.
When the team received this lung, they had experienced two periods of cold ischemia totaling 22.5 hours, plus five hours of clinical EVLP treatment.
After 24 hours in cross circulation, the lung showed functional recovery, the researchers say.
Zachary Kon, director of the NYU Langone Health lung transplant program, who was not involved in the study, commented: ‘As a lung transplant surgeon, I have seen many patients who do not receive the lung transplants they desperately need.
“I find this work intriguing and hope that this technology will make more donor lungs available.”
Academics say there are two possible ways that research could increase the number of lungs available for transplantation.
They could continue to use the existing method to connect human lungs to pigs and improve organs before sending them for transplantation.
Or, critically ill patients already awaiting transplantation with artificial lung support could serve as a cross-circulation host, assuming the role of a pig.
Then the person would receive the lungs which has helped them regain their strength as soon as they have recovered.
“If we could improve the acceptance rate by 20 percent and increase it to an acceptance rate of 40 percent or 50 percent, we would essentially eliminate our waiting list and actually be able to open the transplant to more people,” said Dr. Bacchetta.
The research was published in the journal Nature Medicine.
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