Funding totalling $23.6 million has been announced to establish an international team – led by
Dr. Michael Laflamme at UHN's McEwen Stem Cell Institute – to develop cutting-edge regenerative therapies for heart disease.
The project, titled
Enabling novel cardiac therapies with pluripotent stem cells, is highly collaborative. It was built out of core team of researchers at the McEwen, Toronto General Hospital Research Institute (TGHRI) and the University of Toronto – in total, 22 leading laboratories will be involved across 10 research institutions in four countries (Canada, the United States, the United Kingdom and Israel).
The funding was announced by the Honourable François-Philippe Champagne, Minister of Innovation, Science and Industry, and the Honourable Jean-Yves Duclos, Minister of Health, and will be administered through the Government of Canada's New Frontiers in Research Fund (NFRF) Transformation program.
"We have reached a pivotal point in the field of regenerative medicine with the convergence of new technologies, significant advances in basic research and recent strides towards clinical application," says Dr. Sara Vasconcelos, a Senior Scientist at the Toronto General Hospital Research Institute and a co-principal investigator on the project.
"This funding will enable the big thinking, sharing of knowledge, and interdisciplinary teams needed to push regenerative therapies for heart disease towards the clinic."
Heart disease is the leading cause of death worldwide, accounting for nearly one-third of all deaths globally. Despite this, there are no curative therapies – existing treatments can only ease symptoms or slow disease progression, rather than restore function. Because of this, the median survival for patients with heart failure is just over two years.
The key challenge to developing curative therapies – those that can restore heart function – is that once the adult human heart is damaged, it has a very limited ability to regenerate.
When a heart attack or other injury occurs, the damaged heart tissue is replaced by non-functional scar tissue. This tissue compromises the heart's ability to pump enough blood to supply the body, and can lead to progressive heart failure.
The research project will address these issues by developing new regenerative therapies that aim to replace the damaged heart tissue with new heart muscle made from stem cells. This will be achieved through three different, but complementary experimental strategies:
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Create all the authentic cell types found in the heart. The heart contains heart muscle cells, support cells, immune cells, and specialized cells that are essential for transmitting electrical signals, as well as blood vessels to supply nutrients to the organ. An important goal of this aim is to establish methods for generating these cell types from stem cells in the quantities needed for therapeutic applications.
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"Create better than nature" heart muscle. Using cutting-edge genetic approaches, the team will create heart muscle cells that are better at healing, less prone to causing arrhythmias and able to survive longer when blood supplies are interrupted (which happens during cell and tissue transplantation procedures).
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Use 3D bioprinting to fabricate a neonatal-scale human heart. With advanced printing strategies, the research team will bioprint functional ventricular chambers of the heart, using the different cell types made from stem cells. These bioprinted ventricles will be tested for their ability to function as a biological biventricular pump. If successful, this work could lay the foundation for future treatments for infants who are born with severe heart defects who currently cannot receive a heart transplant due to a lack of neonatal donor organs.
Societal and ethical aspects will be carefully considered and tightly woven into these aims and the project as a whole. Ethicists, decision scientists, and clinicians will collaborate to establish a clear framework to determine when technologies are ready for clinical trials as well as decision aids to help patients better understand the trade-offs of participation.
"The scope of this project is truly exciting. By bringing together biologists, engineers, clinicians, clinical trialists, mathematicians, bioethicists and health economists, we are launching a Canadian-led program that has not been seen before in terms of breadth and potential impact in the field," says Dr. Laflamme, who is also the McEwen Chair in Cardiac Regenerative Medicine and a staff pathologist in the UHN Laboratory Medicine Program.
"As well, we are engaging with the public, health charities and patient advocacy groups to ensure that those who will most immediately be affected by the therapies can watch our progress and directly provide input," adds Dr. Laflamme.
The over 20 laboratories that will contribute to the project include those located at UHN's McEwen Stem Cell Institute and Toronto General Hospital Research Institute, the University of Toronto, the Hospital for Sick Children, the Toronto Metropolitan University, McGill University, the Centre Hospitalier de l'université de Montréal, Carnegie Mellon University (Pennsylvania), George Washington University (Washington D.C.), Technion – Israel Institute of Technology, and the University of Exeter (Devon, England). The project also leverages existing research projects and networks such as the Ted Rogers Centre for Heart Research, Medicine by Design at the University of Toronto, and the Centre for Commercialization of Regenerative Medicine, based in Ontario.
"This project is built on a strong tradition of pioneering stem cell research in Toronto," says Dr. Brad Wouters, UHN Executive-Vice President of Science and Research. "These contributions have led to the discovery of blood-forming stem cells over 50 years ago, as well as the discovery of cancer stem cells close to 30 years ago.
"The success of this project is also built on the unwavering philanthropic support provided by our donors through the UHN Foundation – funding that enabled us to establish the McEwen Stem Cell Institute."
"With this transformative funding from NFRF, our researchers can now build outward from their success to involve new provincial, national and international collaborators," Dr. Wouters adds. "Only through large-scale and team-based interdisciplinary projects like this will we be able to overcome hurdles and move closer to improving the lives of patients."
About NFRF Transformation
The aim of this funding program is to enable large-scale, Canadian-led, interdisciplinary research teams to address a major challenge in order to realize a real and lasting change. Funded projects tackle a well-defined challenge, propose a world-leading approach that differs from current approaches, are interdisciplinary and have the potential to be transformative—leading to a significant change or breakthrough, rather than an incremental advance.
