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Platform technology for maturation of human stem cell derived cardiomyocytes and cardiotoxicity screening

Platform technology for maturation of human stem cell derived cardiomyocytes and cardiotoxicity screening
人类干细胞来源的心肌细胞成熟和心脏毒性筛选的平台技术
批准号:
493737-2016
负责人:
Radisic, Milica
金额:
$7.28万
依托单位:
依托单位国家:
加拿大
项目类别:
Collaborative Health Research Projects
财政年份:
2017
资助国家:
加拿大
项目状态:
已结题
起止时间:
2017-01-01 至 2018-12-31

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中文摘要
翻译
跳动的心脏细胞无法从人类心脏中取样和扩增,因此制药业被迫使用替代方法来评估新药候选物在到达人类之前的安全性和有效性,包括在动物模型中进行评估。动物心脏细胞具有与人类心脏细胞不同的功能特性,因此在临床前测试期间不可能完全捕获药物的正面和负面影响。因此,许多有前途的候选药物在早期就被放弃,一些危险的药物进入人类使用,例如万络,导致约30,000人死亡和50亿美元的定居点。该项目将通过从干细胞开始开发一系列人类心脏组织,彻底改变药物在到达人类之前的测试方式。我们将成熟的组织,使他们类似于成年人的心脏使用电场刺激。我们将设计一个完全惰性的平台,不会吸收或与应用的药物相互作用。它也将与制药和生物实验室中已经使用的设备兼容。独特的是,我们的平台将以非破坏性的方式从单个组织一次读出许多心脏反应。通过观察来自真实的成熟人类心脏组织的这种综合反应,我们将使药物发现过程更有效,最终通过发现更安全和更有效的地毯来节省加拿大制药业的成本和加拿大人的生命。
英文摘要
Beating heart cell cannot be sampled and expanded from human hearts, thus pharmaceutical industry is forced to usealternative methods to assess safety and efficacy of new drug candidates before they reach humans including assessmentin animal models. Animal heart cells have different functional properties than human heart cells, thus it is not possible to fullycapture both positive and negative effects of a drug during pre-clinical testing. As a result, many promising drug candidatesare abandoned early on and some dangerous drugs reach human use e.g. Vioxx that resulted in ~30,000 deaths and$5billion in settlements. This project will revolutionize the way drugs are tested before they reach humans by developing anarray of human heart tissues, starting from stem cells. We will mature the tissues so that they resemble adult human heartusing electrical field stimulation. We will engineer a fully inert platform that does not absorb or interact with the applied drugs.It will also be compatible with the equipment already in use in pharmaceutical and biological labs. Uniquely, our platform willgive readouts of many cardiac responses at once from the single tissue in a non-destructive manner. By looking at thisintegrated response from a real mature human heart tissue, we will make drug discovery process more effective ultimatelysaving cost to Canadian pharmaceutical industry and lives of Canadians by enabling discovery of safer and more effectivedrugs.
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