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诱导多能干细胞在心脏病疾病建模和药物开发中的应用

Applications for Induced Pluripotent Stem Cells in Disease Modelling and Drug Development for Heart Diseases.

作者信息

Nakao Shu, Ihara Dai, Hasegawa Koji, Kawamura Teruhisa

机构信息

Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu, Japan.

Global Innovation Research Organization, Ritsumeikan University, Kusatsu, Japan.

出版信息

Eur Cardiol. 2020 Feb 26;15:1-10. doi: 10.15420/ecr.2019.03. eCollection 2020 Feb.

DOI:10.15420/ecr.2019.03
PMID:32180835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7066852/
Abstract

Induced pluripotent stem cells (iPSCs) are derived from reprogrammed somatic cells by the introduction of defined transcription factors. They are characterised by a capacity for self-renewal and pluripotency. Human (h)iPSCs are expected to be used extensively for disease modelling, drug screening and regenerative medicine. Obtaining cardiac tissue from patients with mutations for genetic studies and functional analyses is a highly invasive procedure. In contrast, disease-specific hiPSCs are derived from the somatic cells of patients with specific genetic mutations responsible for disease phenotypes. These disease-specific hiPSCs are a better tool for studies of the pathophysiology and cellular responses to therapeutic agents. This article focuses on the current understanding, limitations and future direction of disease-specific hiPSC-derived cardiomyocytes for further applications.

摘要

诱导多能干细胞(iPSC)是通过导入特定转录因子对体细胞进行重编程而获得的。它们具有自我更新能力和多能性。人(h)iPSC有望广泛应用于疾病建模、药物筛选和再生医学。从患有突变的患者身上获取心脏组织进行基因研究和功能分析是一种极具侵入性的操作。相比之下,疾病特异性hiPSC是从患有导致疾病表型的特定基因突变的患者体细胞中获得的。这些疾病特异性hiPSC是研究病理生理学和细胞对治疗药物反应的更好工具。本文重点关注疾病特异性hiPSC来源的心肌细胞在进一步应用方面的当前认识、局限性和未来方向。

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本文引用的文献

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Drug Screening in Human PSC-Cardiac Organoids Identifies Pro-proliferative Compounds Acting via the Mevalonate Pathway.人多能干细胞源性心脏类器官中的药物筛选鉴定出通过甲羟戊酸途径起作用的促增殖化合物。
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Hum Cell. 2021 Jul;34(4):1142-1152. doi: 10.1007/s13577-021-00537-9. Epub 2021 Apr 25.
利用人诱导多能干细胞衍生的心肌细胞建立短 QT 综合征模型。
J Am Heart Assoc. 2018 Mar 24;7(7):e007394. doi: 10.1161/JAHA.117.007394.
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Region and cell-type resolved quantitative proteomic map of the human heart.人类心脏的区域和细胞类型分辨定量蛋白质组图谱。
Nat Commun. 2017 Nov 13;8(1):1469. doi: 10.1038/s41467-017-01747-2.
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Sodium channel current loss of function in induced pluripotent stem cell-derived cardiomyocytes from a Brugada syndrome patient.致心律失常性右室心肌病患者诱导多能干细胞衍生心肌细胞钠离子通道电流功能丧失。
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Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes.氟卡尼通过调控安德尔森-塔维尔综合征诱导多能干细胞衍生心肌细胞中的钠钙交换体通量来改善致心律失常性。
Biochem Biophys Rep. 2017 Jan 11;9:245-256. doi: 10.1016/j.bbrep.2017.01.002. eCollection 2017 Mar.
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Modeling Treatment Response for Lamin A/C Related Dilated Cardiomyopathy in Human Induced Pluripotent Stem Cells.人类诱导多能干细胞中与核纤层蛋白A/C相关的扩张型心肌病的治疗反应建模
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Inhibition of CDK5 Alleviates the Cardiac Phenotypes in Timothy Syndrome.CDK5 抑制可减轻 Timothy 综合征的心脏表型。
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Patient-Specific Drug Screening Using a Human Induced Pluripotent Stem Cell Model of Catecholaminergic Polymorphic Ventricular Tachycardia Type 2.使用2型儿茶酚胺能多形性室性心动过速的人诱导多能干细胞模型进行患者特异性药物筛选
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