Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling and Precision Medicine: A Scientific Statement From the American Heart Association.
Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling and Precision Medicine: A Scientific Statement From the American Heart Association.
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DOI：
10.1161/hcg.0000000000000043
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发表时间：
2018-01
期刊：
影响因子：
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通讯作者：
American Heart Association Council on Functional Genomics and Translational Biology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular and Stroke Nursing
中科院分区：
文献类型：
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作者：
Musunuru K;Sheikh F;Gupta RM;Houser SR;Maher KO;Milan DJ;Terzic A;Wu JC;American Heart Association Council on Functional Genomics and Translational Biology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular and Stroke Nursing
诱导多能干细胞（iPSC）为在细胞水平上研究人类生理和疾病提供了前所未有的机会。它们也有可能被用于精准医疗的实践，例如个性化药物测试。本声明全面描述了iPSC系的来源，它们在心血管疾病建模中的用途，它们在精准医学中的用途，以及促进它们在生物医学应用中更广泛使用的策略。人类iPSC具有独特的特性，使其成为研究人类疾病的模型系统：它们是人类起源的，这意味着它们携带人类基因组;它们是多能的，这意味着原则上它们可以分化成任何人体的体细胞类型;它们是干细胞，这意味着它们可以从单个细胞扩展到数百万甚至数十亿个细胞后代。iPSC提供了研究与个体患者遗传匹配的细胞的机会，基因组编辑工具允许引入或校正遗传变异。在使用iPSCs更好地了解心肌病、心律失常、瓣膜和血管疾病以及缺血性心脏病的代谢风险因素方面取得了初步进展。这项有前途的工作仍处于初期阶段。同样，iPSC才刚刚开始用于确定用于细胞来源患者的最佳药物。本声明旨在（1）总结关于使用iPSC进行心血管特征和疾病建模以及治疗筛选的科学现状;（2）确定使用iPSC进行疾病建模和精准医学的机会和挑战;（3）概述将促进iPSC用于生物医学应用的策略。本声明并不旨在解决干细胞作为再生疗法的使用，例如移植到体内治疗缺血性心脏病或心力衰竭。
Induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to study human physiology and disease at the cellular level. They also have the potential to be leveraged in the practice of precision medicine, for example, personalized drug testing. This statement comprehensively describes the provenance of iPSC lines, their use for cardiovascular disease modeling, their use for precision medicine, and strategies through which to promote their wider use for biomedical applications. Human iPSCs exhibit properties that render them uniquely qualified as model systems for studying human diseases: they are of human origin, which means they carry human genomes; they are pluripotent, which means that in principle, they can be differentiated into any of the human body’s somatic cell types; and they are stem cells, which means they can be expanded from a single cell into millions or even billions of cell progeny. iPSCs offer the opportunity to study cells that are genetically matched to individual patients, and genome-editing tools allow introduction or correction of genetic variants. Initial progress has been made in using iPSCs to better understand cardiomyopathies, rhythm disorders, valvular and vascular disorders, and metabolic risk factors for ischemic heart disease. This promising work is still in its infancy. Similarly, iPSCs are only just starting to be used to identify the optimal medications to be used in patients from whom the cells were derived. This statement is intended to (1) summarize the state of the science with respect to the use of iPSCs for modeling of cardiovascular traits and disorders and for therapeutic screening; (2) identify opportunities and challenges in the use of iPSCs for disease modeling and precision medicine; and (3) outline strategies that will facilitate the use of iPSCs for biomedical applications. This statement is not intended to address the use of stem cells as regenerative therapy, such as transplantation into the body to treat ischemic heart disease or heart failure.