論文 - 詳細
| RRC ID | 59823 |
|---|---|
| 著者 | Ito E, Miyagawa S, Takeda M, Kawamura A, Harada A, Iseoka H, Yajima S, Sougawa N, Mochizuki-Oda N, Yasuda S, Sato Y, Sawa Y. |
| タイトル | Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application. |
| ジャーナル | Sci Rep |
| Abstract |
Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs. There were no karyotypic abnormalities during hiPSCs subculture and differentiation. The hiPSC markers TRA1-60 and LIN28 showed the highest sensitivity for detecting undifferentiated hiPSCs among primary cardiomyocytes. Transplantation of hiPSC-CMs with a LIN28-positive fraction > 0.33% resulted in tumor formation in nude rats, whereas no tumors were formed when the fraction was < 0.1%. These findings suggested that combination of these in vitro and in vivo tumorigenecity assays can verify the safety of hiPSC-CMs for cell transplantation therapy. |
| 巻・号 | 9(1) |
| ページ | 1881 |
| 公開日 | 2019-2-13 |
| DOI | 10.1038/s41598-018-38325-5 |
| PII | 10.1038/s41598-018-38325-5 |
| PMID | 30760836 |
| PMC | PMC6374479 |
| MeSH | Animals Carcinogenicity Tests / methods* Cell Differentiation Cell Proliferation Cells, Cultured Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism Karyotype Membrane Glycoproteins / metabolism Myocytes, Cardiac / cytology* Myocytes, Cardiac / metabolism Myocytes, Cardiac / transplantation Neoplasms / etiology RNA-Binding Proteins / metabolism Rats Rats, Nude Transplantation / adverse effects |
| IF | 4.011 |
| 引用数 | 6 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 14 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | 201B7(HPS0063) 253G1(HPS0002) |