| 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
|
| リソース情報 |
| ヒト・動物細胞 |
253G1(HPS0002) |
