Columbia engineers and surgeons revive historic technique, pioneer new technology to recover damaged donor lungs.
A multidisciplinary team led by Gordana Vunjak–Novakovic, Mikati Foundation Professor of Biomedical Engineering and Medical Sciences at Columbia Engineering, and Matt Bacchetta, associate professor of surgery at Columbia University Medical Center and NewYork–Presbyterian has – for the first time – maintained a fully functional lung outside the body for several days. In a study published in the journal Nature Biomedical Engineering, the researchers describe the cross–circulation platform that maintained the viability and function of the donor lung and the stability of the recipient over 36 to 56 hours. They used the advanced support system to fully recover the functionality of lungs injured by ischemia, and made them suitable for transplant.

The team was inspired by the critical need to expand the pool of donor lungs. Transplantation remains the only definitive treatment for patients with end–stage lung disease, but the number of donor lungs is much smaller than the number of patients in need, and many patients die while on the wait list. In addition, lungs quickly lose their function outside the body and during transport: four out of five lungs evaluated at transplant centers are rejected. If these lungs could be kept viable outside the body long enough, it would be possible to improve their function and use them for transplantation.

Over the past five years, Vunjak–Novakovic has been collaborating with Bacchetta and Hans Snoeck, professor of medicine, to investigate how to improve low–quality donor lungs and possibly bioengineer lungs for transplantation. Rather than attempting to build new lungs, they developed strategies to rescue damaged donor lungs. One approach was to use a stem cell therapy of the lung to replace defective cells with new therapeutic cells derived from the transplant recipient. While this technique was applicable to low–quality lungs that are rejected for transplantation, there was a problem: the support of the lung outside the body was too short for the therapeutic cells to start improving lung function.

As often happens, unmet clinical needs inspire new ideas and drive the development of new technologies. The Columbia team realized that “cross circulation” – an abandoned surgical procedure used in the 1960s to exchange blood flow between two patients – could enable long–term support of living organs outside the body by providing critical systemic and metabolic factors that are missing from all current technologies. The team embraced this idea and devised an entirely new approach to support lungs outside the body long enough to enable therapeutic interventions needed to recover their health and normal function.

The team’s breakthrough was realizing that cross–circulation could be re–configured to help recover damaged donor organs. The study’s lead authors, PhD candidate John O’Neill and postdoctoral research fellow Brandon Guenthart, looked at clinical studies from the 1960s that used cross–circulation of blood between a healthy individual and a patient suffering from a critical but potentially reversible illness. Working in Vunjak–Novakovic’s Laboratory for Stem Cells and Tissue Engineering, they developed a radically new technology to support a fully functional lung outside the body for several days.