Using a new experimental technique, a severely damaged lung has now been restored to function.
Unfortunately for people with terminal lung illness, there’s a huge shortage of donor lungs available – and not only because there are not enough donors. The reality is many donor lungs are significantly damaged, which means they’re practically unusable.
In a study recently published in Nature Medicine, scientists have come up with a new experimental technique and restored such a damaged lung back to function – by sharing its circulatory system with that of a living pig (!).
“It is the provision of intrinsic biological repair mechanisms over long-enough periods of time that enabled us to recover severely damaged lungs that cannot otherwise be saved,” say the lead researchers, surgeon Ahmed Hozain and biomedical engineer John O’Neill of Columbia University.
The underlying principle driving the research is similar to an existing donor lung restoration technique called ex vivo lung perfusion (EVLP). The technique involves placing a lung in a sterile dome attached to a ventilator, pump, and filters.
The lung’s temperature is maintained at human body temperature, and a bloodless solution containing oxygen, nutrients, and protein is circulated through it. That circulation, when liquid is pumped through the organ, is the perfusion part.
The EVLP technique has helped save lives by keeping donor lungs stable and even repairing them a little. However, the time window afforded by the technique is somewhat limited – it can only be conducted for up to eight hours, hardly enough for the biological repair functions to kick in.
That’s where the pigs come in. The research team has managed to prolong that time period with pigs, and long years of research.
In 2017, O’Neill led the development of the xenogeneic (cross-species) cross-circulation platform. Two of the researchers involved, biomedical engineer Gordana Vunjak-Novakovic of Columbia University and surgeon Matthew Bacchetta of the Vanderbilt Lung Institute, led a study in which they restored damaged pig lungs by attaching them to other pigs.
Recently, the researchers have successfully used the same technique to repair five damaged human lungs by connecting them to pigs, including one severely injured lung that had failed to recover function using EVLP.
“We were able to recover a donor lung that failed to recover on the clinical ex vivo lung perfusion system, which is the current standard of care,” Vunjak-Novakovic said. “This was the most rigorous validation of our cross-circulation platform to date, showing great promise for its clinical utility.”
The researchers received six donor lungs right after they were rejected for transplantation. The five lungs in the experiment were attached via a jugular cannula to anaesthetised pigs that had been immunosuppressed, to prevent the pig’s immune system from attacking the lungs. The sixth control lung was attached to a pig that was not immunosuppressed.
All of the lungs were subjected to 24 hours of xenogeneic cross-circulation, while researchers were carefully monitoring the physiological and biochemical parameters of the organs.
Before too long, the control lung broke down. It started developing extra fluid, the circulation broke down, while inflammatory and immune markers rose, blood clots formed, and respiratory function fell – all consistent with hyperacute rejection.
The contrast with the experimental lungs couldn’t have been more pronounced. The five lungs all had previously demonstrated injuries, and still, they showed significant improvement in cellular viability, tissue quality, inflammatory response, and respiratory function.
The change in the lung that had previously failed EVLP in particular underwent an incredible turnaround. It had spent a total of 22.5 hours on ice, and received 5 hours of EVLP. After this, the right lung was accepted for transplant, but the left lung was simply too damaged. It had persistent swelling and fluid build-up. Multiple transplant centres had turned it down.
After 24 hours of sharing blood with a pig, however, something happened. The damaged lung started to show signs of repair. It wasn’t a full recovery, yet much more than ever thought possible. According to the researchers, this suggests that their cross-circulation platform could be used in conjunction with EVLP to help restore lungs that EVLP can’t save alone.
For this reason, any clinical use of the technique would require medical-grade animals, which of course wouldn’t be cheap – nonetheless, it’s something that is under investigation for use in xenotransplantation, that is, pigs’ organs being transplanted in human recipients. (This is currently being tested in baboons.)
There is another option though: the human recipients themselves could potentially become the basis for the cross-circulation platform, being attached to the lungs they will themselves receive, and maybe even other kinds of organs one day in the future.
“Modifications to the xenogeneic cross-circulation circuit could enable investigation and recovery of other human organs, including livers, hearts, kidneys and limbs,” the researchers pointed out in their paper.
Will pigs and other animals ultimately enable the recovery of previously unsalvageable donor organs? The researchers envision that xenogeneic cross-circulation could be utilised as both a translational research platform to augment transplantation research and as a biomedical technology to help addresse organ shortage.
So who knows?