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‘We’re making progress; now we want to make a lung that will last forever:’ UHN surgeon-scientist

UHN marks new era in organ preservation with Ex Vivo Lung Perfusion System

‘We’re making progress; now we want to make a lung that will last forever:’ UHN surgeon-scientist

An organ perfusion specialist on UHN's transplant team prepares a set of lungs in the operating room for transplantation.


Sixteen years ago, time was running out for emphysema patient Andy Dykstra. He was on the waiting list for a desperately needed lung transplant.

“I couldn’t do anything,” he recalls. “Imagine putting a straw in your mouth and having to breathe through it, all day. That was my life.”

These days, Dykstra’s life is a different story.

In 2008, he became the first patient to receive a set of donor lungs through UHN’s groundbreaking Toronto Ex Vivo Lung Perfusion (EVLP) System – a medical breakthrough developed at Toronto General Hospital that is now deployed around the world.

“We performed the first successful lung transplant in the world at Toronto General Hospital [in 1983], and the technique for preserving lungs for transplant was developed here as well,” says Dr. Shaf Keshavjee, chief of innovation at UHN and co-inventor of the EVLP System.

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Lung transplant recipient Andy Dykstra with his granddaughter. In 2008, Dykstra became the first patient to receive a set of donor lungs through UHN’s groundbreaking Ex Vivo Lung Perfusion System.Supplied

The hospital now performs more than 200 lung transplants every year – more than double what was previously possible – and EVLP is transforming transplantation, along with using drones and artificial intelligence (AI) to improve the efficacy of organ procedures.

“We showed that lung transplants were possible, but we still face a challenge,” says Dr. Keshavjee. Although some people have lived 20 years or more after a lung transplant, only about half the people who undergo the procedure are still alive after five years.

“Our goal is to fix that. We’re making progress; now we want to make a lung that will last forever,” Dr. Keshavjee says.

In the quest for a longer-lasting lung, UHN’s 140-person lung research team developed methods to modify the genes of donor lungs to avoid being rejected by the recipient patient. The team needed to find a safe method of perfusion – the way a fluid moves through the circulatory system of an organ or tissue.

The dream of keeping an organ alive outside the body goes back to the 15th century and Leonardo da Vinci, who made drawings of organs supported by external systems. In the 1930s, aviator Charles Lindbergh and surgeon Alexis Carrel tried to build organ perfusion devices, but it took until 2008 at UHN for it to become a reality.

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A surgical team in the operating room at Toronto General Hospital performing a lung transplantation.Supplied

“We proved that you could do this – you can modify the genes in the donor lung to make it work better after transplantation and be rejected less. But it took six to nine hours to do this in the organ donor. It wasn’t practical,” Dr. Keshavjee explains.

The UHN team needed to come up with a system that could keep lungs alive for up to 24 hours.

“We had to develop a system to keep lungs outside the body so you could work on them,” Dr. Keshavjee says.

More than 200 lung transplants can be performed each year at UHN's Toronto General Hospital, thanks to its development and implementation of the EVLP System.

The problem was that donor organs traditionally had to be cooled to 4 degrees Celsius to preserve them before transplantation. (Organs are preserved by keeping them cold, but when they are cold, they can’t be treated because their metabolism is too low.)

“EVLP allows us to keep the lung at 37 degrees, which allows us to perform gene therapy to improve the lung,” Dr. Keshavjee says. “We can routinely keep a lung alive for transplant up to 12 hours now, and we’re working toward 24 hours.”

Dr. Marcelo Cypel, surgical director of UHN’s Ajmera Transplant Centre at Toronto General Hospital and co-developer of the EVLP System, looked at further advancing the quest to develop better, longer-lasting donor organs.

“He wanted to know if you can actually change the blood type of a donor organ before transplanting it,” Dr. Keshavjee says.

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Dr. Laura Donahoe (centre), a cardiothoratic surgeon at UHN, gets gowned up with the team before performing a lung transplant.Supplied

In our recent research paper, he showed how we’ve learned how to strip the antigens off the surface of lungs. We can make a blood-type A lung into a type O lung, to make it a universal donor lung,” he explains.

“We’re engineering organs so that they won’t be rejected, we can change the blood type, and we’re looking at ways to sterilize them to clear hepatitis and other infections so that we have an organ with a known, predictable outcome before we transplant,” he says.

UHN has been able to double the number of lung transplants it performs compared with pre-EVLP days, thanks to the team’s ever-increasing ability to innovate, evaluate, sustain and prepare donor lungs. The breakthroughs don’t stop there, though – they are also now working with drones and AI to expand and grow the system.

“We’re using drones to push the boundaries. We’re developing a safe, clean energy and reliable means to move organs across the province of Ontario and across the country,” says Dr. Andrew Sage, a scientist with UHN who works on the drone and AI aspects of EVLP.

“With a drone, you simply need a 12-foot-by-12-foot landing platform. You don’t need a helicopter pad, you don’t have to send a support team along with the organ and you don’t have to deal with traffic. Using battery-powered drones is much better for the environment than flying organs with a plane or helicopter.”

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Members of UHN’s lung transplant team, including Dr. Andrew Sage (second from left) and Dr. Shaf Keshavjee (right), with the Ex Vivo Lung Perfusion System in the research operating room at Toronto General Hospital.Supplied

Dr. Sage says the UHN team partnered with an aviation company to build specialized drones that can fly organs to hospitals safely; his team focused on what technology is needed to keep lungs or other organs safe during the drone journey.

“It required detailed study of all the takeoff and landing sites and test flights. We did a lot of pre-flight testing before the drone even left the ground,” he says. The procedure now is “relatively straightforward,” he adds.

“We know the time it takes to get the organ to the recipient hospital. There are some limits to what drones can do, but the ability to fly hundreds of kilometres – in populated cities and through commercial airspace – is all within reach. We’re also focusing on using AI to help doctors better assess lungs on EVLP,” Dr. Sage says.

“At UHN we have a huge data set that’s unique in all of medicine. We’re able to generate a tremendous amount of data about the organ, and that’s perfect for the development of AI,” he says.

For example, the team is now working on taking all the information from an organ in EVLP, running this data through AI algorithms to predict what is likely to happen to the organ post-operatively.

The team has built an AI model called “InsighTx,” developing it using examples of different post-operative outcomes. Dr. Sage says they have already shown that the ability to perform transplants with good outcomes increases significantly with AI.

We can make a blood-type A lung into a type O lung, to make it a universal donor lung.”

Dr. Shaf Keshavjee, Chief of innovation at UHN and co-inventor of the Toronto Ex Vivo Lung Perfusion System

“What I honestly didn’t expect when we started was that we would actually attain so many of the dreams of breakthroughs we had,” says Dr. Keshavjee. “Some days, our lab meeting discussions would give you goosebumps.”

The development of the Toronto EVLP System was initially completely donor funded through UHN Foundation, launched with a gift from the Albert and Temmy Latner Family Foundation. “When I bring the Latner family to visit, I can introduce them to patients who are alive today directly as a result of their gift,” says Dr. Keshavjee.

That could include Andy Dykstra. Before his transplant, “my time was running out,” he says. “I likely wouldn’t have had the chance to share my life with my granddaughter.” Today, he can.

Advertising feature produced by Globe Content Studio with University Health Network (UHN). The Globe’s editorial department was not involved.

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