| 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
|
| リソース情報 |
| ヒト・動物細胞 |
201B7(HPS0063)
253G1(HPS0002) |
