Grant: Collaborative Health Research Projects

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.