論文 - 詳細
| RRC ID | 52222 |
|---|---|
| 著者 | Iseoka H, Miyagawa S, Fukushima S, Saito A, Masuda S, Yajima S, Ito E, Sougawa N, Takeda M, Harada A, Lee JK, Sawa Y. |
| タイトル | Pivotal Role of Non-cardiomyocytes in Electromechanical and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissue. |
| ジャーナル | Tissue Eng Part A |
| Abstract |
Although engineered cardiac tissues (ECTs) derived from induced pluripotent stem cells (iPSCs) are promising for myocardial regenerative therapy, the appropriate ratio of cardiomyocytes to non-cardiomyocytes is not fully understood. Here, we determined whether ECT-cell content is a key determinant of its structure/function, thereby affecting ECT therapeutic potential for advanced heart failure. Scaffold-free ECTs containing different ratios (25%, 50%, 70%, or 90%) of iPSC-derived cardiomyocytes were generated by magnetic-activated cell sorting by using cardiac-specific markers. Notably, ECTs showed synchronized spontaneous beating when cardiomyocytes constituted ≥50% of total cells, with the electrical-conduction velocity increasing depending on cardiomyocyte ratio; however, ECTs containing 90% cardiomyocytes failed to form stable structures. ECTs containing 25% or 50% cardiomyocytes predominantly expressed collagen and fibronectin, whereas ECTs containing 70% cardiomyocytes predominantly expressed laminin and exhibited the highest contractile/relaxation properties. Furthermore, transplantation of ECTs containing 50% or 70% cardiomyocytes into a rat chronic myocardial infarction model led to a more profound functional recovery as compared with controls. Notably, transplanted ECTs showed electrical synchronization with the native heart under Langendorff perfusion. Collectively, these results indicate that the quantity of non-cardiomyocytes is critical in generating functional iPSC-derived ECTs as grafts for cardiac-regeneration therapy, with ECTs containing 50-70% cardiomyocytes exhibiting stable structures and increased cardiotherapeutic potential. |
| 巻・号 | 24(3-4) |
| ページ | 287-300 |
| 公開日 | 2018-2-1 |
| DOI | 10.1089/ten.TEA.2016.0535 |
| PMID | 28498040 |
| PMC | PMC5792250 |
| MeSH | Cell Differentiation / physiology Cells, Cultured Electrophysiology Flow Cytometry Humans Induced Pluripotent Stem Cells / cytology* Myocardium / cytology* Myocytes, Cardiac / cytology* Tissue Engineering / methods |
| IF | 3.508 |
| 引用数 | 21 |
| 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 | 12 |
| 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) |