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Ischemic heart disease remains the leading cause of death in Canada and worldwide. Modern medical management has improved the prognosis of patients after a myocardial infarction (MI), commonly known as a heart attack, but existing therapies are largely aimed at slowing disease progression rather than restoring lost contractile function. Transplantation of cardiomyocytes (heart muscle cells) produced from human pluripotent stem cells (hPSCs) offers a potential new therapy that could, for the first time, remuscularize and repair the heart.
Drs. Gordon Keller and Michael Laflamme's laboratories are collaborating on the development of novel therapies for post-MI heart failure based on the transplantation of cardiomyocytes into the damaged area of the heart. Our goal is to restore the electrical and contractile function of injured hearts by generating new muscle in the scarred (damaged) area with hPSC-derived cardiomyocytes.
Their laboratories have already made a number of important advances in this area, including the development of efficient protocols to guide hPSCs to generate specialized cardiac subtypes, proof-of-concept transplantation studies with hPSC-derived cardiomyocytes in rodent MI models, and the first direct demonstration that hPSC-derived cardiomyocytes can become electrically integrated and beat synchronously with the host heart tissue. Our ongoing work builds on these successes to advance the development of a viable cell therapy for heart disease.
Current projects in the labs include:
The heartbeat is initiated and regulated by specialized group of cardiomyocytes known as pacemaker cells. Failure of these pacemakers due to either age or disease can result in life-threatening irregular or slow heart rhythm. The current treatment option for these conditions is the implantation of an electronic pacemaker device that takes over control of activating the heartbeat. Although effective, these devices have a number of disadvantages including the need for periodic battery replacement, a risk of lead infections, a lack of communication with the autonomous nervous system and a lack of adaption to growth in paediatric patients. Transplantation of pluripotent stem cell-derived pacemaker cells could overcome these disadvantages and present an attractive future therapy for patients with pacemaker dysfunction.
Dr. Stephanie Protze's lab is using developmental biology-based approaches to establish strategies to guide the differentiation of hPSCs into the two different types of pacemaker cells found in the heart. One goal of these studies is to generate 'biological pacemakers' from these cells that can be transplanted into patients with pacemaker dysfunction. A second goal of Dr. Protze's work is to use these hPSC-derived pacemaker cells to study specific diseases that affect pacemaker function, such as congenital heart block. These studies are carried out in the Petri dish and are aimed at identifying the causes of such diseases and ultimately identifying potential drugs to treat them.
Current projects include: