Lung transplants remain the only hope for patients suffering from end-stage lung disease. Transplants are often preceded by an extensive period on a waiting list because of a donor shortage, a reality aggravated by the fact that around 80% of donor lungs are discarded. Lung tissue is highly susceptible to damage and rapidly loses function when extracted from the body, too often rendering the organs nonviable by the time they are transported and evaluated at transplant centers. A new perfusion technique developed by a team of doctors and biomedical engineers at Columbia University now promises to solve this problem, prolonging the life of donor lungs by 9 times in a porcine model experiment.
Typical ex vivo perfusion devices consist of an isolated system capable of supporting lungs for only about six hours prior to transplantation, as they do not provide all the metabolic factors and essential conditions to truly mimic a lung’s natural environment. To provide such an environment, the team modified an abandoned surgical technique called cross-circulation – in which blood was circulated between two patients – to reroute the recipient’s blood to the donor organ. This, along with careful engineering to control homeostatic parameters such as blood flow and temperature, allowed the treatment of injured lungs and extended their lives up to 56 hours prior to successful transplantation.
The team was faced with numerous challenges in order to successfully simulate a body-like environment, including having to develop a temperature-controlled humidification chamber and water basin to mimic the thoracic cavity. They also fashioned cannulas from donor vessels and designed a dynamic system to help control the blood pressure and flow to the lungs.
Lungs that were immediately put on cross-circulation maintained healthy metabolism and did not exhibit inflammation, showing no decline for 36 hours. Lengthy cold storage (simulating extraordinarily long organ transportation periods) lead to lung injury and declining lung health. However, extended cross-circulation eventually improved lung parameters to acceptable levels. The team also developed a new imaging technique that allowed for the guided delivery of therapeutic microbeads and stem cells, the latter of which showed successful integration into the donor tissue.
This dramatic extension of donor organ viability offers hope to many patients resolved to spend their days awaiting a life-saving organ that may never arrive. This technique can also be potentially applied to other organs, such as livers and kidneys, in high demand or needing repair. Until it is applied clinically, however, cross-circulation can enable research into lung disease, immune interactions, and new therapies.
Here are two time-lapse videos of the perfusion and humidification systems:
More via Columbia University: New Method Rescues Donor Organs to Save Lives…
Article in Nature Biomedical Engineering: Cross-circulation for extracorporeal support and recovery of the lung…