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Severely damaged human lungs successfully recovered using transgenic system.

An extremely common condition rising at an alarming rate due to environmental and lifestyle causal elements, respiratory disease is the third leading cause of death worldwide. Despite the copious amounts of research currently being carried out in this field the only treatment option available to patients suffering from end-stage lung disease is a double or single lung transplant. In turn, the scant nature of treatment for this condition causes incredibly high mortality rates that are increased even further by the limited availability of healthy donor organs. Unfortunately, even as the number of patients waiting to receive a lung transplant continues to rise, only twenty percent of lungs donated for life-saving transplantation meet the functional criteria for transplantation. This is doubly frustrating as many of the conditions rendering donated lungs unacceptable for transplantation are potentially reversible.

The current gold standard technique used to repair damaged organs is to place donor lungs in cold storage before using ex vivo lung perfusion (EVLP), where the donated lungs are perfused with a nutrient-rich liquid and ventilated on a circuit outside of the body for a few hours. However, recovering even marginal quality donor lungs is challenging as lungs cannot survive on EVLP beyond 6 hours, nowhere near long enough to repair severely tainted donor organs.

Now, a study from researchers led by Columbia Engineering demonstrates severely injured donor lungs declined for transplant can be recovered outside the body by a system utilizing cross-circulation of whole blood between the donated lung and an animal host. The team states human lungs unsuitable for transplant can be recovered using their new transgenic cross-circulation system, with the hope it may provide a much larger number of organ transplants to critically ill patients. The study is published in the journal Nature Medicine.

Previous studies show EVLP is presently used to support unviable donor lungs, recovering them to a marginal quality before transplantation. However, EVLP proffers only a limited survival window of six to eight hours for organs outside of the host body, an insufficient amount of time to recover the majority of severely damaged donated lungs. This had led to a small donor lung recovery rate of an already diminutive pool of donated organs.

Recent studies from the group demonstrated the efficacy of a cross-circulation system to regenerate severely damaged swine lungs. The animal’s lungs were successfully kept on cross-circulation support for an unprecedented four days outside of the body. The team also ensured the swine benefactors remained conscious throughout the procedure, safeguarding against any adverse effects which may be caused by anesthesia or recipient immobility. The current study investigates whether human lungs, already declined for transplantation, can be recovered using a transgenic cross-circulation platform. 

The current study perfuses human lungs outside of the body with venous blood from a live swine whilst simultaneously using a mechanical ventilator to provide artificial respiration. A combination of six sets of single and double human lungs rejected for transplantation were used in the study, including a lung that failed to recover on EVLP. The damaged human lungs were kept in cold static storage for extended periods, longer than 24 hours in one case. They were then treated with cobra venom factor to suppress the innate immune response before they were connected to the animal/human cross-circulation circuit. Data findings show the organs experienced a remarkable recovery despite the prolonged time in cold storage without blood circulation. Results show the human lungs were maintained for an encouraging 24 hours on the circuit, during which they experienced improved gas exchange and increased functionality.

The lab states they have successfully recovered unviable donor human lungs using their chimeric organ recovery system which successfully maintained lung integrity and resulted in functional lung recovery. They go on to extrapolate critically ill patients awaiting transplantation could serve as the cross-circulation host to recover an injured donor lung, which they would receive for transplant as soon as the organ recovers. 

The team surmises they have recovered acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, using the cross-circulation of whole blood between ex vivo organs and a Yorkshire swine. For the future, the researchers state they now hope to extend the benefits of their cross-circulation platform to the recovery of other human organs, including hearts, kidneys, whole limbs, and livers.

Source: Columbia Engineering

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