Induced Pluripotent Stem Cell-Derived Cardiomyocytes Provide In Vivo Biological Pacemaker Function

Circulation. Arrhythmia and Electrophysiology
Samuel ChauveauMichael R Rosen

Abstract

Although multiple approaches have been used to create biological pacemakers in animal models, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have not been investigated for this purpose. We now report pacemaker function of iPSC-CMs in a canine model. Embryoid bodies were derived from human keratinocytes, their action potential characteristics determined, and their gene expression profiles and markers of differentiation identified. Atrioventricular blocked dogs were immunosuppressed, instrumented with VVI pacemakers, and injected subepicardially into the anterobasal left ventricle with 40 to 75 rhythmically contracting embryoid bodies (totaling 1.3-2×10(6) cells). ECG and 24-hour Holter monitoring were performed biweekly. After 4 to 13 weeks, epinephrine (1 μg kg(-1) min(-1)) was infused, and the heart removed for histological or electrophysiological study. iPSC-CMs largely lost the markers of pluripotency, became positive for cardiac-specific markers. and manifested If-dependent automaticity. Epicardial pacing of the injection site identified matching beats arising from that site by week 1 after implantation. By week 4, 20% of beats were electronically paced, 60% to 80% of beats were matching, and mean and maxim...Continue Reading

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Citations

Jul 18, 2018·Circulation. Arrhythmia and Electrophysiology·Suraj KapaPaul J Wang
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Methods Mentioned

BETA
xenograft
Chip
fluorescence-activated cell sorting

Software Mentioned

pClamp10
Prism
SigmaPlot
GraphPad
Affymetrix MAS

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