Development of a physiological cardiac microtissue platform for drug development

药物对心脏的不良疗效和不可预测的毒性作用是导致一种药物从市场上被下架的主要原因。许多药物在病人身上的作用不可预测，因为它们是在实验室里用塑料培养皿中生长的细胞和模仿人类的动物身上进行测试的。**改进的心脏组织模型可以在**药物发现过程中更早地识别和消除有毒和无效的药物。为了满足这一需求，我们开发了一种微流控平台，可以模拟人体组织的特征，如血液流动和三维组织排列，比标准细胞培养模型更好。该平台将适用于拉伸和电刺激心脏微组织，以更好地模拟人类心脏生理。我们还开发了一种新的超声成像技术，可以从平台外快速评估心脏显微组织的跳动和收缩。我们建议将这些技术结合起来，开发一种新的改进心脏模型，以快速、方便地评估心脏显微组织的功能。该模型与标准实验室设备和中高通量工作流程的兼容性将是独一无二的，确保以最少的时间和精力轻松实施。**我们将优化新的心脏模型，以实现比目前可能的更类似于天然人类心脏组织的功能，使用患者来源的心脏细胞来模拟正常和患病的心脏组织。在项目完成后，我们将提供一种新的同类最佳的人类心脏组织模型，通过在药物开发过程中比现有方法更早地识别无效和有毒药物，预计将减少与药物开发相关的时间和成本。**该项目将产生由我们的合作伙伴公司和具有跨学科专业知识的学员准备商业化的技术，以领导加拿大生物技术、生物医学和卫生部门的下一代**创新。

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.