A new experimental technique shows how connecting the circulatory system of pigs to damaged human lungs can restore the latter to function, according to a recent paper published in the journal Nature Medicine.
Attaching pigs to damaged human lungs can heal the latter
While respiratory disease is the third-leading cause of deaths worldwide, the only available cure for patients with end-stage lung disease is a lung transplant — a very serious procedure. The medical field has seen significant advances but lung transplantation is still limited by the availability of healthy donor organs — with most available lungs unusable due to severe but potentially-reversible damage.
To date, a method called ex vivo lung perfusion (EVLP) continues to provide lung support outside the body and has seen success helping marginal-quality lungs recover before transplantation. But EVLP only provides a limited timeframe of support, at six to eight hours — too short a period to recover the majority of function in severely damaged donor lungs.
Cross-circulation of damaged lungs with animals
However, a multidisciplinary team from Vanderbilt University and Columbia Engineering has shown how severely-damaged donor lungs that saw declined health during transplant can be restored outside of the body via a system using cross-circulation of blood between the donor lung and an animal host.
This is significant because it means severely-damaged lungs — which typically fail to recover from the standard clinical EVLP — can successfully recover most function after 24 hours on the team's cross-circulation platform.
Significant recovery of severely damaged lungs
Under the joint-leadership of Gordana Vunjak Novakovic, Mitaki Foundation Professor of Biomedical Engineering and Medical Sciences at Columbia Engineering, and Matthew Bacchetta — surgical director of the Vanderbilt Lung Institute — the investigators credited their discovery to the physiologic milieu and systemic regulation that their novel platform can give explanted human lungs.
"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," said the lead authors of the study John O'Neill — an adjunct associate research scientist at Columbia Engineering — and Ahmed Hozain — surgical research fellow at Columbia Engineering.
In the last eight years, the researchers have created a radical new method of providing lungs for patients who face grim consequences without a viable organ transplant. In 2017 they showed how cross-circulation support of whole lungs was feasible outside the body.
In 2020, they extended the viable timeframe of cross-circulation support to an unprecedented four days.
New lower limit for damaged human lungs
The new paper shows how explanted human lungs — already in decline from preparation for transplantation — may be recovered via the team's cross-circulation platform, which successfully maintains lung integrity and restores full lung functionality. During the 24 hours of cross-circulation, the team witnessed a substantial recovery of tissue quality, inflammatory responses, cell viability, and — most significantly — respiratory function.
"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. This was the most rigorous validation of our cross-circulation platform to date, showing great promise for its clinical utility," said Vunjak-Novakovic.
The recovered lung in question had suffered persistent swelling and fluid buildup that were unresolvable, which is why several transplant centers declined to use it for transplantation, leaving it up to research to save it from eventual disposal. When the team finally received the lung, it had experienced two periods of cold ischemia — a sum of 22.5 hours — plus another five hours of clinical EVLP treatment.
Notably, after 24 hours of cross-circulation, the damaged lung experienced significant functional recovery.
This incredible work — using a cross-circulation platform to bring an extremely damaged human lung to full functionality in only 24 hours — was the result of an auspicious and multi-institutional research team — 25 cutting-edge investigators and experts in surgery, stem cells, bioengineering, immunology, and various clinical disciplines. As medical fields continue to advance, we can expect the greatest developments to come from increasingly interdisciplinary collaborations.