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Biochem Biophys Res Commun ; 494(1-2): 138-143, 2017 12 09.
Article in English | MEDLINE | ID: mdl-29042197

ABSTRACT

Microelectrode array (MEA) based-drug screening with human induced pluripotent stem cell-derived cardiomyocytes (hiPSCM) is a potent pre-clinical assay for efficiently assessing proarrhythmic risks in new candidates. Furthermore, predicting sympathetic modulation of the proarrhythmic side-effects is an important issue. Although we have previously developed an MEA-based co-culture system of rat primary cardiomyocyte and sympathetic neurons (rSNs), it is unclear if this co-culture approach is applicable to develop and investigate sympathetic innervation of hiPSCMs. In this study, we developed a co-culture of rSNs and hiPSCMs on MEA substrate, and assessed functional connections. The inter-beat interval of hiPSCM was significantly shortened by stimulation in SNs depending on frequency and pulse number, indicating functional connections between rSNs and hiPSCM and the dependency of chronotropic effects on rSN activity pattern. These results suggest that our co-culture approach can evaluate sympathetic effects on hiPSCMs and would be a useful tool for assessing sympathetic modulated-cardiotoxicity in human cardiac tissue.


Subject(s)
Coculture Techniques/instrumentation , Induced Pluripotent Stem Cells/physiology , Myocytes, Cardiac/physiology , Neurons/physiology , Animals , Arrhythmias, Cardiac/chemically induced , Cardiotoxins/toxicity , Cells, Cultured , Drug Evaluation, Preclinical/instrumentation , Drug Evaluation, Preclinical/methods , Electric Stimulation , Humans , Induced Pluripotent Stem Cells/drug effects , Microelectrodes , Myocytes, Cardiac/drug effects , Neurons/drug effects , Rats
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