Monitoring Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Genetically Encoded Calcium and Voltage Fluorescent Reporters

被引：101

作者：

Shinnawi, Rami ^{[1
,2
]}

Huber, Irit ^{[1
,2
]}

Maizels, Leonid ^{[1
,2
]}

Shaheen, Naim ^{[1
,2
]}

Gepstein, Amira ^{[1
,2
]}

Arbel, Gil ^{[1
,2
]}

Tijsen, Anke J. ^{[1
,2
]}

Gepstein, Lior ^{[1
,2
,3
]}

机构：

[1] Technion Israel Inst Technol, Sohnis Family Lab Cardiac Electrophysiol & Regene, Rappaport Fac Med, IL-3109601 Haifa, Israel

[2] Technion Israel Inst Technol, Res Inst, IL-3109601 Haifa, Israel

[3] Rambam Hlth Care Campus, IL-3109601 Haifa, Israel

来源：

STEM CELL REPORTS | 2015年 / 5卷 / 04期

基金：

欧洲研究理事会;

关键词：

POLYMORPHIC VENTRICULAR-TACHYCARDIA; LONG-QT SYNDROME; ACTION-POTENTIALS; NEURAL ACTIVITY; INDICATORS; NEURONS; CARDIOMYOPATHY; MUTATION; THERAPY; SENSOR;

D O I：

10.1016/j.stemcr.2015.08.009

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The advent of the human-induced pluripotent stem cell (hiPSC) technology has transformed biomedical research, providing new tools for human disease modeling, drug development, and regenerative medicine. To fulfill its unique potential in the cardiovascular field, efficient methods should be developed for high-resolution, large-scale, long-term, and serial functional cellular phenotyping of hiPSC-derived cardiomyocytes (hiPSC-CMs). To achieve this goal, we combined the hiPSC technology with genetically encoded voltage (ArcLight) and calcium (GCaMP5G) fluorescent indicators. Expression of ArcLight and GCaMP5G in hiPSC-CMs permitted to reliably follow changes in transmembrane potential and intracellular calcium levels, respectively. This allowed monitoring short- and long-term changes in action-potential and calcium-handling properties and the development of arrhythmias in response to several pharmaceutical agents and in hiPSC-CMs derived from patients with different inherited arrhythmogenic syndromes. Combining genetically encoded fluorescent reporters with hiPSC-CMs may bring a unique value to the study of inherited disorders, developmental biology, and drug development and testing.

引用

页码：582 / 596

页数：15

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