2018 Fiscal Year Final Research Report
Rapid and Efficient Cardiac Direct Reprogramming using Sendai Virus Vectors
| Project/Area Number |
16K19428
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Keio University |
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Principal Investigator |
MIYAMOTO KAZUTAKA 慶應義塾大学, 医学部(信濃町), 共同研究員 (10528714)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 心筋再生 / direct reprogramming / センダイウイルス |
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| Outline of Final Research Achievements |
In this study, we show that Sendai virus (SeV) vectors expressing cardiac reprogramming factors efficiently and rapidly reprogram both mouse and human fibroblasts into integration-free iCMs via robust transgene expression. SeV-GMT generated 100-fold more beating iCMs than retroviral-GMT and shortened the duration to induce beating cells from 30 to 10 days in mouse fibroblasts. In vivo lineage tracing revealed that the gene transfer of SeV-GMT was more efficient than retroviral-GMT in reprogramming resident cardiac fibroblasts into iCMs in mouse infarct hearts. Moreover, SeV-GMT improved cardiac function and reduced fibrosis after myocardial infarction. Thus, efficient, non-integrating SeV vectors may serve as a powerful system for cardiac regeneration. Finally, we reported these result on one of authoritative scientific journals（Miyamoto et al., Cell Stem Cell 2017).
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| Free Research Field |
心筋再生
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| Academic Significance and Societal Importance of the Research Achievements |
現在全世界において心臓疾患関連死は増加の一途をたどっており、新たな治療法の開発が望まれている。近年、iPS細胞をはじめとした再生医療は様々な領域において実用化に向けた検討がなされている。心疾患の分野においてもその臨床応用が開始されているが、依然として細胞の生着率の問題や安全性の面において克服すべき課題は多い。
その点において、本方法が臨床応用された場合上記のような問題点が一気に解消される可能性があり、学術的および社会的な意義は高いと考える。
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