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For patients with end-stage lung disease a lung transplant is the final treatment that can hope to keep them alive, but, as a donor organ, viable lungs are difficult to come by. A new study published in the journal Nature Medicine details how a surgical team has created a therapy that can recover severely damaged donor lungs outside of the body to create a viable organ that is fit for transplantation by connecting it to the blood supply of a pig.
Led by a team from Columbia Engineering and Vanderbilt University, the researchers wanted to see if they could recover a pair of lungs from a cadaver which at time of removal from the body were not fit for donation. While an existing procedure uses ex vivo lung perfusion (EVLP) to try and achieve this, it can only support the lungs for around six to eight hours outside of the body, which often isn’t enough time to recover the damaged tissue.
The new approach uses cross-circulation of whole blood between the donor lung and an animal host, in this instance pigs. They kept the human lungs perfused with blood by connecting the blood vessels of the organ to the neck veins of a living pig. By filtering the blood through a living animal with functioning organs, harmful substances could be removed from the blood and vital nutrients added in the same way our bodies are constantly altering our blood chemistry to keep our tissues healthy. This improves the longevity of the explanted lungs and their recovery by flushing the organ with healthy, fresh blood while ventilators maintain the lung's function, filling and releasing air as they would do in situ. Amazingly, the process doesn't appear to have a lasting negative effect on the pigs, which in previous versions of the study were awake, moving around, and playing while they facilitated the repair of the lungs.
Using this method, the recovered lung was able to be restored over a 24-hour period on the team's cross-circulation platform by connecting to a living pig to keep the lungs alive. During this time of live animal-supported cross-circulation, the researchers found that the cell viability, tissue quality, and inflammatory responses of the lung tissue improved, as well as, most importantly, their respiratory function. They were later able to use this method to support donor lungs outside of the body for an unprecedented four days.
"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 study's lead authors, Ahmed Hozain, surgical research fellow at Columbia Engineering, and John O'Neill, adjunct associate research scientist at Columbia Engineering, in a statement.
While a promising achievement, it will be some time before the cross circulatory technique is fit for clinical practice, as the safety and possible risks of this method still merit investigation. However, the cross circulatory recovery of damaged organs shows promise as a tool to further study transplant immunology, donor regeneration, and the development of novel therapies to improve the outcomes of such radical surgeries.
