Neuronal control of beating rates in human iPS cell-derived cardiomyocytes

Abstract

Cell based assay is an effective tool for low-cost and high-throughput drug screening. Recently a drug screening system with human iPS cell derived cardiomyocytes (hiPSCM) on a microelectrode array (MEA) was developed and has been widely used for detecting side effects of drugs on cardiac tissues. However, this system can be applied to detection of only direct effects on cardiac tissues but not indirect effects mediated by neurons that innervate cardiac tissues. Here, we developed hiPSCM and rat sympathetic neurons co-culture on MEA. hiPSCM and rat sympathetic neurons were cultured in culture chamber which was combined with MEA. Staining experiments indicated that axons grew and reached at hiPSCM. Electrical stimulation in neurons evoked neuronal activities and induced increase in beat rates of hiPSCM indicating that rat sympathetic neurons innervated functionally hiPSCM. These results suggest that our system enables us to regulate the neuronal control of beating rates in hiPSCM.