The next frontier in transplantation: Canadian researchers develop breakthrough technology with the goal of eliminating organ transplant waitlists
New Frontiers in Research Fund | Published: 2022-03-29 12:00 PM (eastern)
It is an agonizing life that most people would find hard to imagine, but a stark reality for many. Something as simple as a walk across the room can leave them gasping for air, or they can experience exhaustion that is so intense it is nearly impossible for them to get out of bed. For others, the only way to get through the day is to spend hours on dialysis. These are some of the daily struggles that close to five thousand Canadians face each year while waiting for an organ transplant—waiting for the call with the news that doctors have found a lung, kidney, liver, heart or pancreas that is a match.
“I have seen so many people who have literally been at death’s door waiting for a transplant,” says Dr. Atul Humar, Medical Director at the University Health Network’s (UHN’s) Ajmera Transplant Centre, Canada’s largest transplant centre, located in Toronto.
Humar says that, despite years of improvements in donor rates, still less than one quarter of all Canadians are registered donors. Even when organs are donated, up to 80% of them go unused because doctors don’t have sufficient time to investigate the health and viability of the organ before transplant. Even when the organs are healthy, many times there is a compatibility issue, where the recipient and donor blood types don’t match. It means that the sickest person on the list is often passed over because their blood type isn’t a match to the available donor organ. The donor organ will go to the next person in line who is a blood type match. The result is that, each year, only just over half of all Canadians waiting for a transplant will receive one. Tragically, one person will die every 36 hours, waiting for that call. Hundreds of others are too sick to be put on the waitlist in the first place.
“If we can offer lifesaving transplants to more patients, then, for me, that would be an incredible achievement,” adds Humar.
Humar and a team of global experts in transplantation are working to create a world where those barriers to getting a transplant don’t exist. It would be a world where it doesn’t matter what blood type the donor organ is, where doctors will have the ability to make every organ universally compatible, a fit for anyone. It would be a world where doctors have the time needed to rid a donor organ of infection or disease so that it can be healthy enough to transplant. Organs would be retrofitted so perfectly for the patient and their medical needs that there would no longer be a risk of infection or rejection. It would be a world with virtually no transplant waitlist.
“Other researchers have tried, but no one has been successful. Ultimately, somebody has to hit the home run—and we have,” says Dr. Shaf Keshavjee, Surgeon-in-Chief at UHN and Director of the Toronto Lung Transplant Program at the Ajmera Transplant Centre.
Keshavjee and his team have led the world in lung transplantation for decades, and now believe they are on the cusp of revolutionizing the transplant field for all organs.
Even when organs are donated, up to 80% of them go unused because doctors don’t have sufficient time to investigate the health and viability of the organ before transplant.
“I think what we’ll do is get to a point where, if your organ is not functioning, we’ll get you a new one, just like a hip replacement. That’s the way it should be, and I think we can get to that,” says Keshavjee. “This is out-of-this-world game-changing.”
Keshavjee, Humar and a team of transplant surgeons from across the country have been awarded $24 million over six years through the 2020 New Frontiers in Research Fund (NFRF) Transformation stream competition, to develop what promises to be lifesaving and groundbreaking transplant technology. This six-year project, titled The Next Frontier in Transplantation, will build on the team’s 2018 breakthrough invention of the Toronto Ex Vivo Lung Perfusion (EVLP) system. EVLP uses specialized machines to maintain and treat donor lungs outside the body for up to three days before transplant. The system gives surgeons more opportunity to test the lungs for function and viability before transplant, ensuring the best match, and allows for more time to prepare recipients for surgery. EVLP’s innovative technology has resulted in the doubling of lung transplants at Toronto General Hospital, to more than 200 per year, making the hospital the largest lung transplant centre in the world. EVLP is now used internationally, saving lives around the globe.
“If we put a lung on our EVLP system, 70% of the time it results in a lung we can use,” says Keshavjee, the nominated principal investigator on the project. “So now, what about the 30% we can't fix? That’s what this research is all about.”
The NFRF Transformation grant will allow the team to spend the next six years developing the Ex Vivo Organ Perfusion (EVOP) systems—a similar technology to that which they created for lungs—that will now provide a platform to evaluate and treat the liver, kidney, pancreas and heart. In groundbreaking science, the team will work to eliminate infections such as cytomegalovirus, hepatitis C, or pathogenic bacteria in donor organs before transplant, essentially sterilizing the organs, making them healthy and functioning for the recipient. In a world first, the researchers will also attempt to eliminate the necessity for blood type matching, making every organ “universal”, so that it can be used in any patient. This development is based on a discovery by Dr. Marcelo Cypel, co-principal investigator on the project, that is not only considered completely transformative in transplant medicine, but has the potential to save thousands more lives worldwide each year.
“Currently we have to match organs by A, B, O type, and what Dr. Cypel is doing is taking the A and B off so we make a universal organ,” Keshavjee explains. “Whoever needs it could use it. If we can do that, just think of how we can save the people who need it right away.”
“It’s creating a much fairer allocation system, because then you could really select who is on top of the list because they are the sickest, not just because they are a match,” adds Cypel, a thoracic surgeon at UHN and Professor of Surgery at the University of Toronto. “In Canada, for example, if you are B blood type, you will wait on average nine years for a kidney. The same patient who is an O blood type will only wait two years. You can see the massive impact this would have.”
The technology will also have a major impact when it comes to composite tissue (skin, muscle, nerves, vessels) allotransplantation. Dr. Siba Haykal, co-principal investigator on the project and a plastic and reconstructive surgeon at UHN, says the EVOP system will preserve composite tissues outside the body, without blood flow, for a longer period of time. It will allow surgeons, like her, to bioengineer new composite tissues, by removing donor cells and repopulating them with recipient-specific cells. The goal is to make the recipient body think the tissue actually belongs to it. This would be an incredible advance that could eliminate the need for high doses of anti-rejection medication.
The assembly of this interdisciplinary global team creates the greatest chance of sustainably reducing the organ shortage and saving more lives.
“To me, this represents new techniques, where we can really change a person’s life,” says Haykal. “Whether they’ve been disfigured by burns, trauma or cancer, if they’ve had an amputation and need prosthetic limbs, or if they require a new airway, we can provide hope for these patients who currently don’t have many options. If we can use techniques that reduce the amount of anti-rejection medication, and maybe one day get to a stage where they don’t need it anymore, that has a very large impact on patients’ quality of life,” adds Haykal.
The Next Frontier in Transplantation research project includes 28 co-principal investigators and co-applicants from across Canada, the United States and the United Kingdom. Brendan Parent, co-applicant and Assistant Professor in the Division of Medical Ethics at New York University’s School of Medicine, where he is also Director of Transplant Ethics and Policy Research, will focus on how the team can promote trust in transplant research. “We want to ensure the fair allocation of research organs, and we plan to develop authorization and consent practices through community engagement,” says Parent. “My personal goal of this project is to make the public more knowledgeable about the frontier of transplant research, and to have them participate as equals alongside researchers in the advancement of transplantation. The assembly of this interdisciplinary global team creates the greatest chance of sustainably reducing the organ shortage and saving more lives.”
Keshavjee believes this project will transform the field of transplantation, creating a world where every patient is treated with a personalized transplant plan.
“If you are diagnosed with cancer you get a biopsy, and we figure out what the issue is. We don’t treat everyone with the same drug, chemotherapy or surgery; we personalize what we do for each patient,” says Keshavjee. “Transplantation is a relatively young field, and up until now we’ve treated every organ the same way. Now in our labs we can actually use the personalized medicine approach and build new organs pre-prepared for the task. That is the new frontier our research is creating.”
Humar hopes they will one day get to a place where EVOP’s success means hospitals around the world will have to increase capacity to handle the high demand of transplantation. “It would be a great predicament to be in,” he laughs. “I think for all of us in transplant, it would be a dream come true if we had more organs than we knew what to do with.”
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