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用于疾病建模和药物筛选的人诱导多能干细胞衍生心肌细胞及组织工程策略。

Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening.

作者信息

Smith Alec S T, Macadangdang Jesse, Leung Winnie, Laflamme Michael A, Kim Deok-Ho

机构信息

Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.

Toronto General Research Institute, McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, Canada.

出版信息

Biotechnol Adv. 2017 Jan-Feb;35(1):77-94. doi: 10.1016/j.biotechadv.2016.12.002. Epub 2016 Dec 20.

Abstract

Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities.

摘要

目前正在积极寻求改进的方法,以对心脏病表型进行建模,并准确筛选潜在治疗化合物的疗效和毒性,从而推动药物开发并提高疾病建模能力。为此,最近人们投入了大量精力来开发新型工程化仿生心脏组织平台,该平台能够准确再现人类心肌的结构和功能。在心脏工程领域,诱导多能干细胞(iPSC)是一种令人兴奋的工具,具有推动当前技术水平发展的潜力,因为它们源自体细胞,能够制定个性化医疗策略并建立患者特异性疾病模型。在此,我们综述基于iPSC的心脏工程技术的不同方面。我们重点介绍了产生iPSC衍生心肌细胞(iPSC-CM)的方法,并讨论了它们在化合物疗效/毒性筛选以及常见心脏病的体外建模中的应用。特别关注微纳工程技术在新型基于iPSC-CM的平台开发中的应用及其推动当前临床前筛选模式发展的潜力。

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