Biotechnology Focus June/July 2016

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OIRM By Lisa Willemse

ONTARIO

The pace of progress in heart regeneration

Dr. Michael Laflamme is mixing old and new technologies to piece together the right combination of stem cells needed to repair the damaged heart. Heart repair has long been a challenge of modern medicine. Comprised primarily of muscle, the heart is somewhat unique among our organs in that its resident population of stem cells are not terribly active once they’ve finished the job of building the organ prior to birth. As a result, these lazy (the scientific term is quiescent) stem cells don’t jump to action after injury, as is the case in a heart attack. Instead, scar tissue develops from the dead and dying cells, which can place undue strain on other areas of the heart and lead to heart failure and other associated illnesses in the long term. Over the years, two main approaches to dealing with this problem have emerged: the first seeks ways to encourage the resident population of heart stem cells to wake up and repair the tissue, and the second uses heart stem cells grown in the lab that can then be transplanted into the patient. It’s in this second approach that Dr. Michael Laflamme, principal investigator at the McEwen Centre for Regenerative Medicine, has directed his focus. Dr. Laflamme is leading a Disease Team project, funded by the Ontario Institute for Regenerative Medicine (OIRM) that seeks to convert scar tissue left behind after heart attack into new replacement muscle.

The replacement muscle comes in the form of new cardiac cells, grown from stem cells in the lab and then transplanted into the injured heart. Much like a puzzle, each piece requires a certain amount of specialized work, from the uniform type of heart muscle cells required for transplant, to the ability to efficiently scale these cells up into large numbers, and to the use of a new electrical mapping technology to determine what effect the transplanted cells have on the natural rhythm of the recipient heart. To find this level of expertise and infrastructure, Dr. Laflamme, had to pick up his lab and move from America’s west coast to Toronto. He is unequivocal about the wisdom of his move. “Many of the missing pieces for our work in Seattle were already in place here,” said Dr. Laflamme, who is also a member of the Toronto General Research Institute’s Cardiac Pathology team in the University Health Network. “Toronto has world class experts in stem cell biology; people that are working in the same area and are kindred spirits. I’m an applied sort of guy. I want to see these cells put to use fixing injured hearts, and I think we can do it better here than any other place in the world.” In Toronto, Dr. Laflamme has already built on his earlier research conducted at the University of Washington, that, while successful in growing and grafting new heart tissue, showed less than optimal results. The research animals tended to develop arrhythmias (irregular heart rhythm), which Dr. Laflamme speculated was a result of the transplant having contained a mix of different types of heart cells, including pacemaker cells, which began working on their own rhythm rather than that of the host’s heart.

“This is where the imaging capabilities will be very helpful. We can record the electrocardiogram to see if the animal experiences arrhythmias, but we can even go further and we can actually map the electrical activity. ” — Dr. Michael Laflamme Biotechnology Focus / June/July 2016

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