Abstract
Human induced pluripotent stem (iPS) cell-derived cardiomyocytes are used for in vitro pharmacological and pathological studies worldwide. In particular, the functional assessment of cardiac tissues created from iPS cell-derived cardiomyocytes is expected to provide precise prediction of drug effects and thus streamline the process of drug development. However, the current format of electrophysiological and contractile assessment of cardiomyocytes on a rigid substrate is not appropriate for cardiac tissues that beat dynamically. Here, we show a novel simultaneous measurement system for contractile force and extracellular field potential of iPS cell-derived cardiac cell sheet-tissues using 500 nm-thick flexible electronic sheets. It was confirmed that the developed system is applicable for pharmacological studies and assessments of excitation-contraction coupling-related parameters, such as the electro-mechanical window. Our results indicate that flexible electronics with cardiac tissue engineering provide an advanced platform for drug development. This system will contribute to gaining new insight in pharmacological study of human cardiac function.
Highlights
Parameters that must be measured in in vitro drug studies using human pluripotent stem (PS) cell-derived cardiomyocytes can be classified into two general categories: electrophysiological parameters and contractility
A system has recently been developed that combines technologies in tissue engineering and flexible electronics to allow monitoring of extracellular field potentials on dynamically beating cardiac tissues created from human PS cell-derived cardiomyocytes.[12]
The results indicate that the dynamic beating of cultured cardiac cell sheet-tissues on the flexible electronics does not affect the extracellular field potential waveforms
Summary
Parameters that must be measured in in vitro drug studies using human PS cell-derived cardiomyocytes can be classified into two general categories: electrophysiological parameters and contractility. We show a novel system that simultaneously measures contractile force and extracellular field potential of dynamically beating cardiac cell sheet-tissues. Cardiac cell sheet-tissues generate wrinkles on the flexible electronics corresponding to their beating To investigate whether such wrinkle affects the electrodes' properties, thereby creating artifacts in the extracellular field potential waveform, changes in electrode impedance were measured after subjecting the flexible electronics to a compressive strain of 20% (Fig. 2c). The results indicate that the dynamic beating of cultured cardiac cell sheet-tissues on the flexible electronics does not affect the extracellular field potential waveforms. The result suggest that the choice of extracellular field potential has little effect on the results of EMW evaluation
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