Grant: Collaborative Health Research Projects (NSERC partnered)

Poor efficacy and unpredictable toxic effects of drugs on the heart are leading causes of removal of a drug from the market. Many drugs act unpredictably in patients because they are tested 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 in the drug discovery process. To meet this need, we have developed a microfluidic platform that can model features of tissues in the body, like blood flow and three-dimensional tissue arrangement, better than can be done with standard cell culture models. This platform will be adapted to stretch and electrically stimulate heart microtissues to better simulate human heart physiology. We have also developed a new ultrasound imaging technique that can rapidly assess heart microtissue beating and contraction from outside the platform. We propose to combine these techniques to develop a new and improved heart model to rapidly and easily assess the function of heart microtissues. This model will be unique in its compatibility with standard laboratory equipment and medium- to high-throughput workflow, ensuring ease of implementation with minimal time and effort. We will optimize the new heart model to achieve functionality more similar to native human heart tissue than currently possible, using patient-derived heart cells to model normal and diseased heart tissue. At project completion, we will deliver a new best-in-class model of human heart tissue that is expected to decrease the time and cost associated with drug development by identifying ineffective and toxic drugs much earlier in the drug development process than is possible with current methods. This project will produce technologies that are primed for commercialization by our partner companies and trainees with interdisciplinary expertise to lead the next generation of innovations in the Canadian biotechnology, biomedicine, and health sectors.