Grant: Collaborative Health Research Projects (NSERC partnered)

During human clinical trials, a large percentage of candidate drugs fail because they are unsafe or ineffective. Even when pre-clinical cell and animal studies seem positive, problems occur because tests done with drugs on these models are often not predictive of what happens in humans. Much of this is due to significant differences in biology between species. For instance, ion channels (membrane proteins through which heart cells conduct electrical currents) can vary between humans and animals. Many drugs, including non-cardiovascular drugs, target these ion channels in the heart, which can potentially result in lethal arrhythmias. Thus, it is critical to use preclinical models that can closely reproduce what happens in humans to better predict drug safety. To streamline the therapeutic development pipeline, we will develop a novel 3D bioprinted human cardiac tissue model which will improve the translational science process for predicting whether drugs will be safe and effective in humans. The goal is to develop 3D human cardiac tissue structure(s) that closely model the electrophysiological properties of the human heart, relevant to impulse conduction and arrhythmia generation. We will use commercially available human induced-pluripotent stem cells (hiPSC)-derived cardiomyocytes and novel microfluidic based 3D bioprinting technology and methodologies to build the 3D cardiac tissue. Ultimately, these models are expected to replace the use of animals to screen drugs for safety and efficacy. To validate our models, we will evaluate the cardiotoxicity potential of a range of known compounds, and compare the outcome with data obtained using current standard assays. It takes on average over $2.5 billion to develop and gain marketing approval for a new drug. About $100 million is required to complete the pre-clinical studies alone. Using novel bioprinted models of cardiac tissue is expected to significantly cut the cost and time of bringing a new drug to market.