A ‘Potent’ Treatment For Damaged Hearts

What was science fiction a decade ago could soon be reality: rebuilding failing hearts with pluripotent stem cells.

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Based on the most recent data from 2012/13, 63,200 Canadian adults had a first heart attack that year. According to heart pathologist Michael Laflamme, professor of laboratory medicine and pathobiology at the University of Toronto, about a quarter of these cases will progress to some degree of heart failure. Therapies don’t yet exist to treat these failing hearts.

“We can treat the symptoms, we can attenuate the disease process, but we don’t have really any way to replace the muscle that’s damaged in a heart attack other than to give somebody a whole new heart,” says Laflamme. “And we know there’s not enough of those to go around.”

During a heart attack, there is a blockage in the blood vessels that feed the heart, and downstream of that blockage, the heart muscle that loses access to blood dies. A major obstacle in heart repair is the scar tissue that eventually forms to replace the lost heart muscle.

Laflamme, also a researcher at the University of Toronto’s Medicine by Design, works with pluripotent stem cells that have the potential to repair the heart after a heart attack.

“Our vision is to use stem cells to repopulate or remuscularize that scar tissue, to make it back into functional muscle,” says Laflamme.

Laflamme can already make heart muscle from pluripotent stem cells, but every day his team works to make their process even better, and to continue to refine their cell therapy so that patients can benefit.

“This is what I consider big science, things that would have seemed like science fiction when we were starting this work back in 2002,” adds Laflamme. “I’m really excited that it’s become so tangible. We really would like to get to a first-in-human study with a new stem cell-based therapy for heart disease, in something like a 4-5 year time horizon.”

If successful, Laflamme hopes to bring this therapy to clinical trials in as few as 10 years, turning an idea that once sounded like science fiction into a mainstream therapy.

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Michael Laflamme is the Robert McEwen Chair in Cardiac Regenerative Medicine at University Health Network and a Senior Scientist in the Toronto General Hospital Research Institute. After obtaining an undergraduate degree in Physics at Georgetown University, Laflamme completed the Medical Scientist (MD/PhD) Training Program at Emory University, where he studied the regulation of calcium homeostasis by beta-adrenergic signaling in adult ventricular cardiomyocytes. After residency in Anatomic Pathology and subspecialty training in cardiovascular pathology at the University of Washington Medical Center, he completed a postdoctoral fellowship in the laboratory of Dr. Charles Murry, investigating the role of exogenous and endogenous stem cells in myocardial repair. 

His independent research career has been largely focused on the development of cell therapies based on human embryonic stem cells (hESCs), and his laboratory has made a number of important contributions in this area including: widely-used protocols to guide the differentiation of hESCs and induced pluripotent stem cells into cardiomyocytes and specialized cardiac subtypes (e.g. ventricular myocytes versus pacemaker cells); the first proof-of-concept study showing that the transplantation of hESC-CMs can “remuscularize” scar tissue and improve left ventricular contractile function in rodent MI models; and the first direct demonstration that grafts of hESC-CMs can electrically couple with host myocardium following transplantation in injured hearts.

Laflamme has been the recipient of honours including the Society for Cardiovascular Pathology Young Investigator Award, the Perkins Coie Award for Discovery and the ASGCT Outstanding New Investigator Award. He is also a board-certified physician in Anatomic Pathology and practices diagnostic cardiovascular pathology. 

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