A new system that keeps lungs viable and breathing after removing them from an organ donor has helped doctors boost successful lung transplants by 50 percent.
A new system that keeps lungs viable and breathing after removing them from an organ donor has helped doctors boost successful lung transplants by 50 percent. It is one of several perfusion systems now in development that promise to revolutionize how donor organs are stored and distributed.
Around the world, patients waiting for organ transplants far outnumber the number of donated organs. Yet finding more organ donors solves only half of the problem, because donated organs are often underutilized. This is because doctors do not have enough time to assess how well an organ is functioning before it loses viability and cannot be transplanted. As a result, only the healthiest organs are shipped to patients, and many potentially useful hearts, livers, kidneys—and especially lungs—are discarded after harvesting.
A new generation of medical devices that keeps those organs functioning outside the body could change that. These ex vivo organ perfusion machines condense a room full of equipment into a machine that clinicians can wheel next to a table in an operating room.
After removing the organ, the physicians connect it to the machine, which pumps oxygenated blood through it to keep it viable. Physicians can then monitor its condition, attempt to improve its function with medicines or other treatments, and prepare it to minimize immune response when transplanted into another patient.
Ultimately, the ability to keep organs alive outside the body will give physicians greater latitude in how they match organs with patients. They might, for example, seek matches that reduce the likelihood of immune system rejection, or direct the healthiest organs to the youngest patients, who will need to rely on them for many decades. Keeping organs alive ex vivo would also give hospitals more time to schedule a top surgical team for each transplantation, instead of rushing to put a team together as soon as an organ arrives.
The idea of ex vivo organ perfusion has been alive since Leonardo da Vinci sketched an idea in his notebooks. In 1935, aviator Charles Lindberg and Nobel Prize winning physician Alexis Carrel built a glass perfusion pump that kept cat and bird organs viable at body temperature for 21 days.
Of the eight organs available for donation, lungs are the most underutilized. Worldwide, about 80 percent of donor lungs go unused because it is hard for doctors to assess the function and viability of the tissue. Prior to donation, lungs may accumulate fluid, blood clots, or experience damage from mechanical ventilation. Moreover, the risk of transplanting compromised lungs is high: If a transplanted pair of lungs does not work properly, the recipient usually dies.
But now, an ex vivo lung perfusion system developed at the University of Toronto helps doctors at Toronto General Hospital transplant 50 percent more donor lungs than they could before.
In 2011, the team led by physicians Shaf Keshavjee and Marcelo Cypel of the University of Toronto, conducted the first clinical trial for ex vivo lung perfusion. This followed years of development, since they needed to create a perfusion system that did not damage the lungs while keeping them alive at normal body temperatures. According to Keshavjee, the team has published case studies of 340 lung transplants that used the system.
At first, the equipment needed to keep a lung viable filled an entire room. Working with an engineering team, the researchers recently rolled out an automated system the size of a dishwasher that was simpler to operate, improved outcomes due to built-in quality systems, and was scalable.
The system has doctors place donor lungs in a sterile chamber warmed to body temperature. The lungs are then connected to a ventilator, which pumps oxygen into the lungs, and a centrifugal pump, which acts as an artificial heart to pump a combination of red blood cells and STEEN solution through the lungs. STEEN solution consists of human serum albumin, a protein that keeps blood volume (and pressure) constant; dextran to coat and protect lung tissue from forming clots; and an electrolyte that prevents free radical formation that can lead to vascular spasms.
The STEEN solution takes the place of blood. Functioning lungs inhale oxygen and transfer it to the circulating fluid, exchanging it with carbon dioxide that they then exhale, just as they would naturally in a body. After the fluid leaves the lungs, it passes through a gas exchange membrane to deoxygenate it and replenish it with carbon dioxide before it reenters the lungs. Doctors can assess lung function by testing the amount of oxygen in the fluid leaving the lungs and knowing the amount introduced through ventilation.
This system can keep lungs alive outside of the body for 12 hours, 36 times longer than the time lungs remain vital after a patient dies. In experiments, the machine has kept lungs alive for close to 24 hours, and researchers hope to extend it to a week, Keshavjee said. While on external support, doctors can examine the tissue with fiber optic cameras and treat infection, blood clots, and fluid accumulation with medicine.
Keshavjee, director of the Toronto lung transplant program, is also testing a method to treat donor lungs with gene therapy during perfusion to improve lung function and reduce rejection after transplant. The process involves packaging genetic information for a protein called interleukin-10 inside an adenovirus shell.
This protein helps repair lungs from inflammation that occurs prior to donation. It also prepares the lungs for the recipient’s immune system by preloading them with a protein that reduces the recipient’s immune response. He recently tested the approach in experiments with pig lung transplants and he hopes to take it to human clinical trials within the next six months.
Keshavjee said the ex vivo lung perfusion system was successful because his team focused only on building a machine with the functions needed to keep lungs operating properly. He is chief scientific officer at XOR Labs Toronto, a university spinoff founded to commercialize the perfusion system. He hopes to market a commercial version of the automated lung perfusion machine within in a year. He has already lined up several hospitals to run clinical tests.
His second company, Perfusix, was recently purchased in the US by Lung Bioengineering, which operates an organ repair center in Silver Spring, MD. His vision is that after harvesting lungs, hospital surgeons will chill and ship them to the facility, where they will be placed on life support, treated to improve outcomes, and distributed to surgical teams around the country.
Keshavjee also argues that he can apply the same strategy used to keep lungs alive to building machines to perfuse livers, kidneys, and hearts.
He will have company. The companies Tevosol and Transmedics are developing all-purpose machines for lung, liver, kidney, and heart transplants. Other researchers and companies are developing machines to preserve and repair specific organs.
It is a competition that anyone waiting for an organ transplant will win.
Melissae Fellet is a science writer based in Missoula, MT.
Read more about organ transplants on AABME.org.