論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 253G1(HPS0002) |