Contractility evaluation using human induced pluripotent stem cell-derived cardiomyocytes

<p>[Background & Purpose] Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are anticipated to be useful tools for evaluating cardiotoxicity. In particular, there is great interest in evaluating myocardial contractility by using hiPS-CMs, because some anticancer drugs affect this contractility. We evaluated the contractility of hiPS-CMs by using the FLEXcyte96 (FLEX; Nanion Technologies), a tool newly introduced for contractility assay. In FLEX, cells are cultured on thin membranes and contractility is measured as the movement of the membranes. It is anticipated that hiPS-CMs will acquire a mature-like phenotype upon culture on thin membranes mimicking the mechanical environment of heart tissue. In this study, we investigated the culture conditions suitable for this assay and compared FLEX with impedance measurement by using CardioExcyte96 (CE; Nanion Technologies), a conventional method of observing contraction. [Methods & Results] We purchased two different hiPS-CM lines (Cell lines A, B). The cells were cultured for 7 days and their contractility measured by using FLEX. Also, we compared laminin and fibronectin as extracellular matrices for culture. Cell line A cultured with fibronectin contracted steadily. Next, we measured contractility and impedance by using FLEX and CE, respectively. Positive inotropic effects were detected by FLEX, but not with CE. [Discussion] We identified culture conditions suitable for FLEX assay. One possible reason for detection of the positive inotropic effect is that the hiPS-CMs were matured by culture on thin membranes.</p>