Calcium and voltage mapping in hiPSC-CM monolayers

• Human pluripotent stem cells offer a new approach to study human cardiac biology, including intracellular calcium flux.
• Unlimited numbers of human cardiomyocytes can be generated from pluripotent stem cells.
• hiPSC-CM monolayers offer a personalized medicine approach to study cardiac arrhythmias.
• Multi-parametric imaging of hiPSC-CM monolayer voltage and calcium flux enables comprehensive human arrhythmia testing.

The advent of induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) has revolutionized the cardiovascular research field. Now it is possible to generate a virtually unlimited supply of patient specific pluripotent stem cells and cardiomyocytes that can be used for research purposes, drug toxicity testing and/or regenerative medicine therapies. The most immediate application for this technology is in vitro disease modeling and in vitro drug toxicity testing. To date the majority of disease modeling and drug toxicity testing has been performed on single hiPSC-CMs in culture. However, the study of complex cardiac arrhythmia mechanisms requires a more physiological model system of electrically and mechanically connected hiPSC-CMs that function as a syncytium-like the cardiomyocytes of the adult heart. This review focuses on the work that has been performed recently using hiPSC-CM 2D monolayers for the study of cardiac electrical impulse propagation.

Electrical activation maps of spontaneous and electrically paced propagation in human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) monolayers. (A) Spontaneous activity in dish 1. The spatial distribution of the activation timing, derived from maximum voltage upstroke velocity, with isochronal lines at each 2-ms interval. (B) Electrically stimulated (at the monolayer center) activity in dish 1. The spatial distribution of the activation timing, derived from maximum voltage upstroke velocity, with isochronal lines at each 2-ms interval. The 2 white circles are separated by a 5-mm distance. At a pacing frequency of 2 Hz, it took 24.9 ± 2.3 ms (from 3 stimulations) for the activation wave to propagate from the inner to the outer circle. This translates to a conduction velocity of 20.1 cm/s−1 for this monolayer. Scale bar: 5 mm C, hiPSC-CM monolayers contain atrial (MLC2a+) and ventricular (MLC2v+) cardiomyocytes.Figure optionsDownload as PowerPoint slide