Lung transplantation, the only lifesaving therapy for an increasing population of patients with end-stage lung disease, is severely limit by the number of available donor organs. Currently, up to 80% of donor lungs are reject for serious but potentially reversible injuries. Since the beginning of transplantation in the 1960s, clinicians and scientists have been trying to address the critical shortage of donor organs.
Now, a multidisciplinary team from Columbia Engineering and Vanderbilt University has for the first time demonstrate in a clinically relevant model that severely damage lungs can be regenerate to meet transplantation criteria. In a study publish today on Nature Communications ‘ website, the researchers describe the cross-circulation platform that maintain the viability and function of the donor lung and the stability of the recipient for 36 to 56 hours.
To support lung recovery
As Brandon Guenthart, a lead author of the study, explains; hence to support lung recovery and to demonstrate cellular regeneration; They had to pursue a radically different approach and develop more minimally invasive diagnostics. Current methodologies of lung support are limited to only 6 to 8 hours, a time that is too short for therapeutic interventions that could regenerate the injured lung and improve its function.
The team, co-led by Gordana Vunjak-Novakovic, University Professor and The Mikati Foundation Professor of Biomedical Engineering and Medical Sciences at Columbia Engineering, and Matthew Bacchettaunjak-Novakovic, the H. William Scott Professor of Surgery at Vanderbilt University, and adjunct professor at Columbia’s department of biomedical engineering; hence also develop new diagnostic tools for the non-invasive evaluation of the regenerating lung.
The researchers have long been focused on developing processes to recover lungs; so that are turn down for transplant because of injury to enable people with end-stage lung disease to live longer and better lives. They have fortunate to assemble a highly talented, interdisciplinary team of bioengineers, surgeons; who have design a durable physiologic support system; so for a donor lung outside the body; hence along with new technologies to achieve and monitor lung recovery.
The cross circulation platform
A previous study from the team demonstrated a cross circulation platform; so that maintain the viability and function of a donor lung for 36 hours. The researchers were able to use their advanced support system to fully recover; so the functionality of lungs injured by ischemia (restricted blood supply) and make them suitable for transplant.
For this new study, the team decide to test the effectiveness of their platform technology; so combine with conventional therapies and new diagnostics on lungs; so afflict by the most frequent injury leading to donor lung rejection gastric aspiration. This injury is caused by the entry of gastric material into the respiratory tract; so resulting in severe injury to the pulmonary epithelium and thus making the lung unacceptable for transplantation.
Currently, severely damaged donor lungs cannot be salvaged using existing devices or methods. This new study suggests that lungs injure by gastric aspiration can be maintain outside the body for several days; so are amenable to repeated therapeutic interventions; also display evidence of cellular regeneration and improved function. Lungs regenerated on this platform met all criteria for transplantation.
This paper represents a culmination of fundamental and translational studies of lung bio engineering; so that have converge into a system capable to recover severely damaged lungs. The team plans to conduct further studies to evaluate the functional capacity of the lungs following transplantation and the safety of the method; so using a clinically relevant large animal model with immunosuppression.