UHN and U of T receive $24-million federal grant for transplant research

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 U of T’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."

 

Atul Humar, director of the Ajmera
Transplant Centre
(photo by Tim Fraser)

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 U of T and director of the Ajmera Transplant Centre at UHN.

Funding ground-breaking innovation

Brad Wouters, UHN's executive vice president, science and research, notes that this major grant will enable multidisciplinary teams to develop new, cutting-edge approaches to extend the time that donated organs can be used, and also enable treatment and repair of unsuitable organs to allow treatment of more patients.

It will also help the teams refine and improve equitable organ allocation guidelines for all patients, he adds.

“The advancements that this team has made and their continued success is made possible by support from provincial and federal governments, industry partners, external charitable agencies, generous philanthropy from the UHN Foundation and our incredible patient partners,” says Wouters, who is also a professor in the department of radiation oncology at U of T. “This award recognizes the tireless efforts of the team, and this support, which have been key to achieving global impact.”

The New Frontiers Research Fund was designed to support large-scale, Canadian-led interdisciplinary research projects with the potential to realize real and lasting change.

The fund falls under the strategic direction of the Canada Research Coordinating Committee and is administered by the Tri-Agency Institutional Programs Secretariat on behalf of Canada's three research granting agencies: the Social Sciences and Humanities Research Council, the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council.

Personalized medicine for every organ and beyond

Over the course of this project, the team of over 20 researchers at U of T, UHN, national and international partner sites will develop sophisticated ex vivo platforms to:

• 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 U of T 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 U of T.

"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.