| RRC ID |
68030
|
| 著者 |
Tadano K, Miyagawa S, Takeda M, Tsukamoto Y, Kazusa K, Takamatsu K, Akashi M, Sawa Y.
|
| タイトル |
Cardiotoxicity assessment using 3D vascularized cardiac tissue consisting of human iPSC-derived cardiomyocytes and fibroblasts.
|
| ジャーナル |
Mol Ther Methods Clin Dev
|
| Abstract |
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 negative inotropic drugs, verapamil reduced both MCS and ADD (61% at 100 nM). Thus, this 3D cardiac tissue detected the expected effects of various cardiovascular drugs, suggesting its usefulness for cardiotoxicity evaluation.
|
| 巻・号 |
22
|
| ページ |
338-349
|
| 公開日 |
2021-9-10
|
| DOI |
10.1016/j.omtm.2021.05.007
|
| PII |
S2329-0501(21)00091-7
|
| PMID |
34514026
|
| PMC |
PMC8408525
|
| IF |
4.533
|
| リソース情報 |
| ヒト・動物細胞 |
253G1(HPS0002) |
