New York, NY – July 13, 2020 – Respiratory disease is the third leading cause of death worldwide, and lung transplantation remains the only cure for patients with end-stage lung disease. Despite advances in the field, lung transplantation remains limited by the low availability of organs from healthy donors, and most donor lungs cannot be used due to serious but potentially reversible injuries. Currently, a method known as ex vivo Pulmonary perfusion (EVLP) is used to provide lung support outside the body and to recover lungs from marginal quality donors before transplantation. However, EVLP provides only a limited duration of six to eight hours of support, a time that is too short to recover most of the lungs from severely damaged donors.
A multidisciplinary team at Columbia Engineering and Vanderbilt University has shown that the lungs of severely injured donors who have been rejected for transplantation can be recovered outside the body by a system that uses cross-circulation of whole blood between the donor’s lung and a animal host. For the first time, a severely injured human lung that was unable to recover using standard clinical EVLP was successfully recovered for 24 hours on the team’s cross-circulation platform. The study is published today in Natural medicine.
The researchers, led by Gordana Vunjak-Novakovic, a university professor and professor at the Mikati Foundation for Biomedical Engineering and Medical Sciences at Columbia Engineering, and Matthew Bacchetta, Surgical Director of the Vanderbilt Lung Institute, attributed the achievement of their greatest milestone to the physiological environment. . and systemic regulation that its unique platform provides to explanted human lungs.
“It is the provision of intrinsic biological repair mechanisms for long enough periods of time that allowed us to recover severely damaged lungs that would not otherwise be salvageable,” said study lead authors Ahmed Hozain (a surgical researcher at Columbia Engineering) and John O’Neill (Associate Investigator Research Fellow at Columbia Engineering).
For the past eight years, researchers have been developing their radically new method of providing more lungs to patients who urgently need an organ transplant. In 2017, they demonstrated the feasibility of supporting cross-circulation of entire lungs outside the body. In 2019, they demonstrated the effectiveness of cross circulation by regenerating severely damaged pig lungs, and in 2020, they successfully extended the duration of cross circulation support to an unprecedented four days.
Now in this new paper, the team shows that explanted human lungs, already rejected for transplantation, can be recovered on their cross-circulation platform, which successfully maintained lung integrity and resulted in functional lung recovery. Throughout the 24-hour cross circulation, the team observed substantial improvements in cell viability, tissue quality, inflammatory responses, and most importantly, respiratory function.
“We were able to recover a donor lung that was not recovered in the ex vivo pulmonary perfusion clinical 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.
This particular donor lung demonstrated persistent inflammation and fluid buildup that could not be resolved, and was rejected for transplantation by multiple transplant centers 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. Surprisingly, after 24 hours in cross circulation, the lung showed functional recovery.
Video showing the sequence of lung recovery in the cross circulation system.
Vunjak-Novakovic noted that the size and profile of his multi-agency research team – 25 researchers with expertise in bioengineering, surgery, immunology, stem cells and various clinical disciplines – reflects the complexity of this translation project.
Zachary Kon, Director of the Lung Transplant Program, NYU Langone Health, 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 needed. This work is intriguing to me and I hope this technology will make more donor lungs available. “
The researchers emphasize that more work needs to be done before cross-circulation becomes a clinical reality. For the clinical application of the cross circulation platform, they envision two clinical scenarios for the application of the cross circulation platform, which they plan to follow. One approach is to directly translate the method demonstrated in this new study, with the human donor lung recovered by “xenogeneic” cross circulation with a medical grade pathogen free animal host. To this end, it will be necessary to assess the safety, feasibility, risk profiles, and outcomes of xenogeneic cross circulation in large numbers of lungs.
Another approach is that critically ill patients already awaiting transplantation with artificial lung support could serve as a cross-circulation host to recover an injured donated lung, which they would receive for transplantation as soon as the organ recovers. As described in the document, the xenogeneic cross circulation platform can also serve as a research tool to investigate organ regeneration, transplant immunology, and the development of new therapies.
Looking to the future, the researchers hope to extend the benefits of their cross-circulation platform to the recovery of other human organs, including livers, hearts, kidneys, and limbs.
###
Columbia Engineering
Columbia Engineering, based in New York City, is one of the best engineering schools in the US and one of the oldest in the nation. Also known as the Fu Foundation School of Engineering and Applied Sciences, the School expands knowledge and advances technology through the pioneering research of its more than 220 professors, while educating undergraduate and graduate students in a Collaborative environment to become informed leaders with a firm foundation in Engineering. The school’s faculty is at the heart of the University’s interdisciplinary research, contributing to the Institute of Data Science, the Earth Institute, the Zuckerman Mind Brain Behavior Institute, the Precision Medicine Initiative, and the Columbia Nano Initiative. Guided by its strategic vision, “Columbia Engineering for Humanity”, the school aims to translate ideas into innovations that foster a sustainable, healthy, safe, connected and creative humanity.
