Cardiotoxicity assessment using 3D vascularized cardiac tissue consisting of human iPSC-derived cardiomyocytes and fibroblasts.

Molecular Therapy. Methods & Clinical Development
Kiyoshi TadanoYoshiki Sawa


Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are used for cardiac safety assessment but have limitations for the evaluation of drug-induced contractility. Three-dimensional (3D) cardiac tissues are similar to native tissue and valuable for the assessment of contractility. However, a longer time and specialized equipment are required to generate 3D tissues. We previously developed a simple method to generate 3D tissue in a short period by coating the cell surfaces with extracellular matrix proteins. We hypothesized that this 3D cardiac tissue could be used for simultaneous evaluation of drug-induced repolarization and contractility. In the present work, we examined the effects of several compounds with different mechanisms of action by cell motion imaging. Consequently, human ether-a-go-go-related gene (HERG) channel blockers with high arrhythmogenic risk caused prolongation of contraction-relaxation duration and arrhythmia-like waveforms. Positive inotropic drugs, which increase intracellular Ca2+ levels or myocardial Ca2+ sensitivity, caused an increase in maximum contraction speed (MCS) or average deformation distance (ADD) (ouabain, 138% for MCS at 300 nM; pimobendane, 132% for ADD at 3 μM). For neg...Continue Reading

Related Concepts

Related Feeds


Cardiotoxicity refers to the muscle damage or dysfunction of heart electrophysiology caused by drug intake or due to disease complications. It is a well-known side effect of several cytotoxic drugs, especially of the anthracyclines and can lead to long term morbidity. Here is the latest research.


Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.