| RRC ID |
56590
|
| 著者 |
Takeda M, Miyagawa S, Fukushima S, Saito A, Ito E, Harada A, Matsuura R, Iseoka H, Sougawa N, Mochizuki-Oda N, Matsusaki M, Akashi M, Sawa Y.
|
| タイトル |
Development of In Vitro Drug-Induced Cardiotoxicity Assay by Using Three-Dimensional Cardiac Tissues Derived from Human Induced Pluripotent Stem Cells.
|
| ジャーナル |
Tissue Eng Part C Methods
|
| Abstract |
An in vitro drug-induced cardiotoxicity assay is a critical step in drug discovery for clinical use. The use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is promising for this purpose. However, single hiPSC-CMs are limited in their ability to mimic native cardiac tissue structurally and functionally, and the generation of artificial cardiac tissue using hiPSC-CMs is an ongoing challenging. We therefore developed a new method of constructing three-dimensional (3D) artificial tissues in a short time by coating extracellular matrix (ECM) components on cell surfaces. We hypothesized that 3D cardiac tissues derived from hiPSC-CMs (3D-hiPSC-CT) could be used for an in vitro drug-induced cardiotoxicity assay. 3D-hiPSC-CT were generated by fibronectin and gelatin nanofilm coated single hiPSC-CMs. Histologically, 3D-hiPSC-CT exhibited a sarcomere structure in the myocytes and ECM proteins, such as fibronectin, collagen type I/III, and laminin. The administration of cytotoxic doxorubicin at 5.0 μM induced the release of lactate dehydrogenase, while that at 2.0 μM reduced the cell viability. E-4031, human ether-a-go-go related gene (hERG)-type potassium channel blocker, and isoproterenol induced significant changes both in the Ca transient parameters and contractile parameters in a dose-dependent manner. The 3D-hiPSC-CT exhibited doxorubicin-sensitive cytotoxicity and hERG channel blocker/isoproterenol-sensitive electrical activity in vitro, indicating its usefulness for drug-induced cardiotoxicity assays or drug screening systems for drug discovery.
|
| 巻・号 |
24(1)
|
| ページ |
56-67
|
| 公開日 |
2018-1-1
|
| DOI |
10.1089/ten.TEC.2017.0247
|
| PMID |
28967302
|
| PMC |
PMC5757089
|
| MeSH |
Antibiotics, Antineoplastic / adverse effects
Cardiotoxicity
Cardiotoxins / adverse effects*
Cell Survival
Cells, Cultured
Doxorubicin / adverse effects
Drug Evaluation, Preclinical / methods*
Humans
Induced Pluripotent Stem Cells / cytology*
Muscle Contraction / drug effects*
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / metabolism
Myocytes, Cardiac / pathology*
|
| IF |
3.508
|
| 引用数 |
18
|
| リソース情報 |
| ヒト・動物細胞 |
253G1(HPS0002) |
