The Canadian “Dream Team” Building the Heart of the Future

New Frontiers in Research Fund | Published:

The Vasconcelos lab will focus on producing lab-made blood vessels to support regenerative therapies for heart disease. Featured above are researcher Sara Vasconcelos (top left) and postdoctoral researcher Sonia Taib (bottom middle), as well as equipment that can be used to 3D bioprint engineered cardiac tissues
Photo: UHN's StRIDe team

When Michael Laflamme enters his Toronto research lab and peers at a petri dish of tiny, beating heart muscle cells that were created from stem cells, he glimpses a world where they form the “heart of the future.”

“It’s something that captures your imagination,” says Laflamme, who is a senior scientist at the University Health Network’s (UHN) McEwen Stem Cell Institute, Robert McEwen Chair in Cardiac Regenerative Medicine, Canada Research Chair in Cardiovascular Regenerative Medicine, and a professor in the University of Toronto’s Department of Laboratory Medicine and Pathobiology. “The cells are doing something you can see with the naked eye. It’s visceral.”

In Canada, heart disease is the second leading cause of death, after cancer. Every year, about 70,000 Canadians suffer a heart attack. The median survival period after heart failure is just over two years.

Everybody's unified by this goal of trying to develop these regenerative therapies.

Existing treatments can only ease symptoms or slow down heart disease; they can’t repair the heart.

Laflamme is the principal investigator on a project to develop new regenerative therapies to replace damaged heart tissue with new heart muscle made using pluripotent stem cells. Scientists are excited about pluripotent stem cells, because they can self-renew and develop into any and all cell types in a body. This means they can potentially produce any cell or tissue the body needs to repair itself.

The team Laflamme leads includes experts from 10 research institutions in four countries, representing six diverse disciplines. Their work is being supported by the Government of Canada’s New Frontiers in Research Fund, and is one of six projects to receive a nearly $24 million Transformation grant in 2022.

Pictured are just a few of the members of the research team, including (left to right) Sara Vasconcelos, Stephanie Protze and lead investigator Michael Laflamme

Pictured are just a few of the members of the research team, including (left to right) Sara Vasconcelos, Stephanie Protze and lead investigator Michael Laflamme
Photo: UHN's StRIDe team

“We’ve put together the ‘Dream Team’ to do this. It’s the only way this was going to succeed,” Laflamme says. “Everybody's unified by this goal of trying to develop these regenerative therapies. We have folks like me who are stem cell biologists, we have engineers, people who have expertise in manufacturing, mathematicians so we can do computational modelling of all kinds of tissues that we’re creating and how the body might respond to them, ethicists, as well as health economists.”

The project has three different but complementary tracks. The first is to create all the authentic cell types found in the heart, and to establish ways to generate them from stem cells in the quantities needed to apply them in therapies. The second is to create heart muscle cells that are “better than nature,” which is to say better at healing themselves than the original human heart cells are. The third is to apply the team’s tissue engineering expertise to construct a neonatal-scale human heart, using various cell types made from stem cells.

The third aim is its most ambitious, according to principal investigator Sara Vasconcelos, a senior scientist at the Toronto General Hospital Research Institute cross-appointed with the University of Toronto’s Institute of Biomedical Engineering. She is an expert on utilizing and developing tissue engineering approaches to address cardiovascular problems. To successfully engineer tissues to fabricate human heart chambers that are the size of a newborn’s, she is excited about utilizing 3D bioprinting technology.

“I think we have reached a pivotal point in regenerative medicine, where we really have a shot at making meaningful contributions,” Vasconcelos says. “And this is really what this grant is about, bringing together the expertise of all these different areas to really push the field forward.”

One of those experts is Carnegie Mellon University scientist Adam Feinberg, another principal investigator on the project. Building on Feinberg’s groundbreaking work in 3D bioprinting the human heart, the researchers will look to scale it up in size.

“The reason we set our goal to make something that was human neonatal-sized is that one of the applications for this technology that we can envision down the road is infants that are born with severe and sometimes inoperable congenital heart disease,” Laflamme says. “We've involved paediatric cardiothoracic surgeons at SickKids hospital here in Toronto and this has really sparked their imagination about how this might be useful down the road.”

Many people don't know that Canada is where stem cells were discovered, here in Toronto, so we've always kind of punched above our weight in stem cell biology.

About 1 in 80-100 Canadian children are born with congenital heart disease. About 90% of these children survive to adulthood.

A big emphasis of the program is getting the research into position for a clinical trial. This includes careful oversight of data collection right from the very beginning by experts like Terrence Yao, a cardiac surgeon at Toronto General who has led past clinical trials, including clinical trials that were related to cardiac stem cell biology.

“We think we have some strategic advantages, in part because of the large depth of experience in stem cell biology in Canada,” Laflamme says. “Many people don't know that Canada is where stem cells were discovered, here in Toronto, so we've always kind of punched above our weight in stem cell biology.”

Working across international borders and across disciplines comes with some challenges, Laflamme acknowledges.

“But everybody’s really excited to come together and roll up their sleeves and get working on this,” he says.

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