UHN and University of Toronto receive $24-million federal grant for transplant research

Led by Shaf Keshavjee, a research team at UHN and U of T received $24 million fr

Led by Shaf Keshavjee, a research team at UHN and U of T received $24 million from Canada’s New Frontiers in Research Fund to advance technology to repair and rebuild organs for transplant (photo by Tim Fraser)

Researchers at University Health Network (UHN) and the University of Toronto have received $24 million to advance technology to repair and rebuild organs outside the body for patients in need.

The project, led by  Shaf Keshavjee , is one of only seven across Canada selected to receive funding in the Government of Canada New Frontiers in Research Fund (NFRF) - Transformation competition , following an international consultation.

"The Ex Vivo Lung Perfusion (EVLP) system we developed here in Toronto has revolutionized lung transplantation in the past decade. Now, it’s been translated around the world to increase lung transplant access and it’s being extended to other organs," says Keshavjee, a professor and vice-chair for innovation in the department of surgery in University of Toronto’s Temerty Faculty of Medicine who is surgeon-in-chief at UHN and a senior scientist at Toronto General Hospital Research Institute.

"With this transformative grant, we now have the opportunity to take ex vivo technology to the next level, where we can repair and rebuild organs for transplant."

Over 4,500 people in Canada are currently waiting for an organ transplant, and more than 270 die each year as the need for transplant greatly exceeds availability.

Ex vivo perfusion systems use specialized machines to maintain, evaluate and treat organs before transplant. They have a huge impact on increasing the number of organs that can be considered for transplant.

The Toronto Lung Transplant Program, led by Keshavjee, has used this technology to double the number of lung transplants performed and lives saved at UHN.

"The New Frontiers grant will allow us to advance applications for lungs and further develop ex vivo systems for other organs, such as liver, kidney, heart and pancreas," says Atul Humar , a co-principal investigator on the project, professor in the department of medicine at University of Toronto and director of the Ajmera Transplant Centre at UHN.

  • Increase organ preservation from hours to days
  • Improve the immune response and organ tolerance for transplant recipients
  • Advance precision medicine to customize organs to each individual patient’s needs

Longer ex vivo preservation prior to transplant will enable many world-first therapeutic applications that will, ultimately, create more organs for clinical transplant.

One example is to use gene therapy to make an organ more like the recipient’s cells and help to address the current hurdle of organ rejection by the immune system. Researchers at UHN are also working on changing an organ’s blood type so the sickest people can get access to the next available organ, instead of waiting for one that exactly matches their blood - a delay that currently can take several months before a match is found.

Another transformative goal is to use medicines and light therapies in the ex vivo circuit to eliminate viral or bacterial infections that previously prevented an organ to be considered for transplant.

"This grant gives us a unique opportunity to extend personalized medicine to every organ group," says  Marcelo Cypel , a professor in the department of surgery at University of Toronto and surgical director of the Ajmera Transplant Centre, who is also a co-principal investigator on the project.

"Not only will it enable longer preservation, this research will let us treat and improve organs. It has the potential to change the paradigm in the field of transplantation."

The change will include several advanced applications, such as the engineering of new organs using stem cells with the goal to make organs available for all in need. Significant progress has already been made in generating new kidneys, lungs and tracheae (windpipe), and their applications will be tested further during the six-year project term.

With the involvement of a multidisciplinary team housed in a world-class centre at UHN, the project will bring personalized medicine to transplant, and go beyond solid organs.

Siba Haykal (photo by Rob Caruso)

Siba Haykal , plastic and reconstructive surgeon and project co-principal investigator, will lead research involving vascularized composite allotransplantation - the transplant of limbs, face, trachea and composite tissues, such as skin and muscles.

"These are very delicate tissues that can’t survive outside the body for very long and are very susceptible to rejection," she explains, adding that the current treatment involves high doses of life-long anti-rejection medication for transplant recipients.

Haykal and the team want to develop a system to preserve limbs and tissues out of the body without blood flow for longer periods. This will enable the application of new cell therapies to ’adapt’ these tissues to the recipient prior to surgery.

"Whether they have been disfigured by burns or from trauma or cancer, if they’ve had an amputation and need prosthetic limbs or if they require a new airway, transplantation provides hope for these patients who currently don’t have many options," says Haykal, who is an assistant professor in the department of surgery at University of Toronto.

"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 would have a huge impact on the patient’s quality of life."

Humar adds, "I have seen so many people who have literally been at death’s door and have been completely turned around by transplant and live a full and healthy life. If we can offer that to more patients, then for me that would be an incredible achievement.

"This funding will also help us disseminate our knowledge, and facilitate other hospitals across Canada and around the world build upon what we’re doing at UHN."

This story was  originally posted on the University Health Network website.

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