02384nas a2200313   4500000000100000000000100001008004100002260001500043653002700058653002800085653003500113100001900148700002000167700001700187700001500204700002000219700001600239700001900255700001900274700001500293700001400308700002300322245012600345856005500471300001000526490000700536520151300543022001402056       2020                            d  c2020-11-0510aBiomedical Engineering10aCardiovascular Diseases10ainduced pluripotent stem cells1 aMosha Abulaiti1 aYaxiaer Yalikun1 aKozue Murata1 aAsako Sato1 aMustafa M. Sami1 aYuko Sasaki1 aYasue Fujiwara1 aKenji Minatoya1 aYuji Shiba1 aYo Tanaka1 aHidetoshi Masumoto00aEstablishment of a heart-on-a-chip microdevice based on human iPS cells for the evaluation of human heart tissue function  uhttps://www.nature.com/articles/s41598-020-76062-w  a192010 v103 aHuman iPS cell (iPSC)-derived cardiomyocytes (CMs) hold promise for drug discovery for heart diseases and cardiac toxicity tests. To utilize human iPSC-derived CMs, the establishment of three-dimensional (3D) heart tissues from iPSC-derived CMs and other heart cells, and a sensitive bioassay system to depict physiological heart function are anticipated. We have developed a heart-on-a-chip microdevice (HMD) as a novel system consisting of dynamic culture-based 3D cardiac microtissues derived from human iPSCs and microelectromechanical system (MEMS)-based microfluidic chips. The HMDs could visualize the kinetics of cardiac microtissue pulsations by monitoring particle displacement, which enabled us to quantify the physiological parameters, including fluidic output, pressure, and force. The HMDs demonstrated a strong correlation between particle displacement and the frequency of external electrical stimulation. The transition patterns were validated by a previously reported versatile video-based system to evaluate contractile function. The patterns are also consistent with oscillations of intracellular calcium ion concentration of CMs, which is a fundamental biological component of CM contraction. The HMDs showed a pharmacological response to isoproterenol, a β-adrenoceptor agonist, that resulted in a strong correlation between beating rate and particle displacement. Thus, we have validated the basic performance of HMDs as a resource for human iPSC-based pharmacological investigations.  a2045-2322