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Review
. 2012 Oct-Nov;110(2-3):166-77.
doi: 10.1016/j.pbiomolbio.2012.07.013. Epub 2012 Aug 7.

Cardiomyocytes derived from human induced pluripotent stem cells as models for normal and diseased cardiac electrophysiology and contractility

Affiliations
Review

Cardiomyocytes derived from human induced pluripotent stem cells as models for normal and diseased cardiac electrophysiology and contractility

Adriana Blazeski et al. Prog Biophys Mol Biol. 2012 Oct-Nov.

Abstract

Since the first description of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), these cells have garnered tremendous interest for their potential use in patient-specific analysis and therapy. Additionally, hiPSC-CMs can be derived from donor cells from patients with specific cardiac disorders, enabling in vitro human disease models for mechanistic study and therapeutic drug assessment. However, a full understanding of their electrophysiological and contractile function is necessary before this potential can be realized. Here, we review this emerging field from a functional perspective, with particular emphasis on beating rate, action potential, ionic currents, multicellular conduction, calcium handling and contraction. We further review extant hiPSC-CM disease models that recapitulate genetic myocardial disease.

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Figures

Fig. 1
Fig. 1
Voltage and calcium optical mapping of cord blood-derived hiPSC-EBs. (A) Voltage mapping. a. Phase image of CBiPSC6.2 EB at 4× magnification. b. Voltage map. hEB was stained with di-4-ANEPPS (voltage-sensitive fluorescent dye), and electrically field-stimulated (arrows indicate direction of electrical wave propagating across EB). c. Action potentials during 0.5 Hz field stimulation. d. Average conduction velocity (CV) measurements (mean ± standard deviation) for control and 15 min after addition of 50 µM isoproterenol during 0.5 Hz field stimulation. (B) Calcium mapping. a. Phase image of beating EB at 4× magnification. b. Calcium map (arrows indicate direction of calcium wave propagating across beating EB). c. Representative calcium transient (Ca) waveforms during 0.5-Hz field stimulation. In both A and B, the white square in a and b denote site of recording in c. Adapted from (Burridge et al., 2011).
Fig. 2
Fig. 2
Immunocytochemistry for cardiac markers in hEB differentiated from CBiPSC6.2 cell line. Adapted from (Burridge et al., 2011).

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