Development of a physiological cardiac microtissue platform for drug development

点击翻译按钮获取中文摘要

Poor efficacy and unpredictable toxic effects of drugs on the heart are leading causes ofremoval of a drug from the market. Many drugs act unpredictably in patients because they aretested in labs using cells grown in plastic dishes and in animals that poorly mimic humans.Improved heart tissue models could identify and eliminate toxic and ineffective drugs earlier inthe drug discovery process.To meet this need, we have developed a microfluidic platform that can model features oftissues in the body, like blood flow and three-dimensional tissue arrangement, better than canbe done with standard cell culture models. This platform will be adapted to stretch andelectrically stimulate heart microtissues to better simulate human heart physiology. We havealso developed a new ultrasound imaging technique that can rapidly assess heart microtissuebeating and contraction from outside the platform. We propose to combine these techniquesto develop a new and improved heart model to rapidly and easily assess the function of heartmicrotissues. This model will be unique in its compatibility with standard laboratory equipmentand medium- to high-throughput workflow, ensuring ease of implementation with minimal timeand effort.We will optimize the new heart model to achieve functionality more similar to native humanheart tissue than currently possible, using patient-derived heart cells to model normal anddiseased heart tissue. At project completion, we will deliver a new best-in-class model ofhuman heart tissue that is expected to decrease the time and cost associated with drugdevelopment by identifying ineffective and toxic drugs much earlier in the drug developmentprocess than is possible with current methods.This project will produce technologies that are primed for commercialization by our partnercompanies and trainees with interdisciplinary expertise to lead the next generation ofinnovations in the Canadian biotechnology, biomedicine, and health sectors.