論文 - 詳細
| RRC ID | 54902 |
|---|---|
| 著者 | Kono K, Sawada R, Kuroda T, Yasuda S, Matsuyama S, Matsuyama A, Mizuguchi H, Sato Y. |
| タイトル | Development of selective cytotoxic viral vectors for concentration of undifferentiated cells in cardiomyocytes derived from human induced pluripotent stem cells. |
| ジャーナル | Sci Rep |
| Abstract |
Cell-processed therapeutic products (CTPs) derived from human pluripotent stem cells (hPSCs) have innovative applications in regenerative medicine. However, undifferentiated hPSCs possess tumorigenic potential; thus, sensitive methods for the detection of residual undifferentiated hPSCs are essential for the clinical use of hPSC-derived CTPs. The detection limit of the methods currently available is 1/105 (0.001%, undifferentiated hPSCs/differentiated cells) or more, which could be insufficient for the detection of residual hPSCs when CTPs contain more than 1 × 105 cells. In this study, we developed a novel approach to overcome this challenge, using adenovirus and adeno-associated virus (AdV and AAV)-based selective cytotoxic vectors. We constructed AdV and AAV vectors that possess a suicide gene, iCaspase 9 (iCasp9), regulated by the CMV promoter, which is dormant in hPSCs, for the selective expression of iCasp9 in differentiated cells. As expected, AdV/CMV-iCasp9 and AAV/CMV-iCasp9 exhibited cytotoxicity in cardiomyocytes but not in human induced pluripotent stem cells (hiPSCs). The vectors also induced apoptosis in hiPSC-derived cardiomyocytes, and the surviving cells exhibited higher levels of hPSC marker expression. These results indicate that the AdV- and AAV-based cytotoxic vectors concentrate cells expressing the undifferentiated cell markers in hiPSC-derived products and are promising biological tools for verifying the quality of CTPs. |
| 巻・号 | 9(1) |
| ページ | 3630 |
| 公開日 | 2019-3-6 |
| DOI | 10.1038/s41598-018-36848-5 |
| PII | 10.1038/s41598-018-36848-5 |
| PMID | 30842516 |
| PMC | PMC6403330 |
| MeSH | Adenoviridae / genetics* Adenoviridae Infections / virology Cell Differentiation* Dependovirus / genetics* Genetic Vectors / administration & dosage* Genetic Vectors / genetics Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism Induced Pluripotent Stem Cells / virology Myocytes, Cardiac / metabolism Myocytes, Cardiac / pathology* Myocytes, Cardiac / virology Parvoviridae Infections / virology Regenerative Medicine* |
| IF | 4.011 |
| 引用数 | 1 |
| 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 | 5 |
| 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 | 201B7(HPS0063) |