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Human Heart Cardiomyocytes in Drug Discovery and Research: New Opportunities in Translational Sciences.
Current Pharmaceutical Biotechnology ( IF 2.2 ) Pub Date : 2020-06-30 , DOI: 10.2174/1389201021666191210142023
Najah Abi-Gerges 1 , Paul E Miller 1 , Andre Ghetti 1
Affiliation  

In preclinical drug development, accurate prediction of drug effects on the human heart is critically important, whether in the context of cardiovascular safety or for the purpose of modulating cardiac function to treat heart disease. Current strategies have significant limitations, whereby, cardiotoxic drugs can escape detection or potential life-saving therapies are abandoned due to false positive toxicity signals. Thus, new and more reliable translational approaches are urgently needed to help accelerate the rate of new therapy development. Renewed efforts in the recovery of human donor hearts for research and in cardiomyocyte isolation methods, are providing new opportunities for preclinical studies in adult primary cardiomyocytes. These cells exhibit the native physiological and pharmacological properties, overcoming the limitations presented by artificial cellular models, animal models and have great potential for providing an excellent tool for preclinical drug testing. Adult human primary cardiomyocytes have already shown utility in assessing drug-induced cardiotoxicity risk and helping in the identification of new treatments for cardiac diseases, such as heart failure and atrial fibrillation. Finally, strategies with actionable decision-making trees that rely on data derived from adult human primary cardiomyocytes will provide the holistic insights necessary to accurately predict human heart effects of drugs.



中文翻译:

药物发现和研究中的人心脏心肌细胞:转化科学的新机会。

在临床前药物开发中,准确预测药物对人心脏的作用至关重要,无论是在心血管安全性方面,还是出于调节心脏功能以治疗心脏病的目的。当前的策略具有明显的局限性,由于有假阳性反应,心脏毒性药物可以逃脱检测或放弃了可能的挽救生命的疗法。因此,迫切需要新的和更可靠的翻译方法来帮助加快新疗法的开发速度。在人类供体心脏的恢复研究和心肌细胞分离方法方面的新努力,为成人原代心肌细胞的临床前研究提供了新的机会。这些细胞表现出天然的生理和药理特性,克服了人工细胞模型,动物模型所带来的局限性,并具有为临床前药物测试提供出色工具的巨大潜力。成年人类原代心肌细胞已经显示出可用于评估药物引起的心脏毒性风险,并有助于确定心脏病,心力衰竭和心房纤颤等心脏病的新疗法。最后,具有可操作决策树的策略将依赖于成年人类原代心肌细胞的数据,将提供准确预测药物对人类心脏的影响所必需的整体见解。成年人类原代心肌细胞已经显示出可用于评估药物引起的心脏毒性风险,并有助于确定心脏病,心力衰竭和心房纤颤等心脏病的新疗法。最后,具有可操作决策树的策略将依赖于成年人类原代心肌细胞的数据,将提供准确预测药物对人类心脏的影响所必需的整体见解。成年人类原代心肌细胞已经显示出可用于评估药物引起的心脏毒性风险,并有助于确定心脏病,心力衰竭和心房纤颤等心脏病的新疗法。最后,具有可操作决策树的策略将依赖于成年人类原代心肌细胞的数据,将提供准确预测药物对人类心脏的影响所必需的整体见解。

更新日期:2020-08-17
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