Grant: Collaborative Health Research Projects

During human clinical trials, a large percentage of candidate drugs fail because they areunsafe or ineffective. Even when pre-clinical cell and animal studies seem positive, problemsoccur because tests done with drugs on these models are often not predictive of whathappens 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 electricalcurrents) can vary between humans and animals. Many drugs, including non-cardiovasculardrugs, 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 inhumans to better predict drug safety.To streamline the therapeutic development pipeline, we will develop a novel 3D bioprintedhuman cardiac tissue model which will improve the translational science process forpredicting whether drugs will be safe and effective in humans. The goal is to develop 3Dhuman cardiac tissue structure(s) that closely model the electrophysiological properties of thehuman heart, relevant to impulse conduction and arrhythmia generation. We will usecommercially available human induced-pluripotent stem cells (hiPSC)-derived cardiomyocytesand novel microfluidic based 3D bioprinting technology and methodologies to build the 3Dcardiac tissue.Ultimately, these models are expected to replace the use of animals to screen drugs forsafety and efficacy.To validate our models, we will evaluate the cardiotoxicity potential of a range of knowncompounds, 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 novelbioprinted models of cardiac tissue is expected to significantly cut the cost and time ofbringing a new drug to market.