Novel 3D bioprinted human cardiac tissue models for drug safety and efficacy testing

用于药物安全性和功效测试的新型 3D 生物打印人体心脏组织模型

• 批准号: 523528-2018
• 负责人: Fedida, David
• 金额: $ 8.1万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=650556
• 关键词: Novel; 3D; bioprinted; human; cardiac

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.

在人体临床试验中，很大比例的候选药物失败是因为它们不安全或无效。即使临床前的细胞和动物研究似乎是积极的，问题也会发生，因为在这些模型上进行的药物测试通常不能预测人类的情况。这在很大程度上是由于物种之间的生物学差异。例如，离子通道（心脏细胞传导电流的膜蛋白）在人类和动物之间可能会有所不同。许多药物，包括非心血管 ** 药物，靶向心脏中的这些离子通道，这可能导致致命的心律失常。因此，至关重要的是使用临床前模型，可以密切复制在人类中发生的事情，以更好地预测药物安全性。为了简化治疗开发流程，我们将开发一种新型的3D生物打印人类心脏组织模型，这将改善预测药物在人类中是否安全有效的转化科学过程。目标是开发3D** 人类心脏组织结构，该结构紧密模拟 ** 人类心脏的电生理特性，与脉冲传导和心律失常产生相关。我们将使用 ** 市售的人类诱导多能干细胞（hiPSC）衍生的心肌细胞 ** 和基于新型微流体的3D生物打印技术和方法来构建3D** 心脏组织。最终，这些模型有望取代使用动物来筛选药物的安全性和有效性。为了验证我们的模型，我们将评估一系列已知 ** 化合物的心脏毒性潜力，并将结果与使用当前标准测定获得的数据进行比较。平均需要超过25亿美元来开发和获得新药的上市批准。仅完成临床前研究就需要大约1亿美元。使用新的心脏组织生物打印模型有望显著降低新药上市的成本和时间。