| Project/Area Number |
17H06724
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Shinshu University |
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Principal Investigator |
Kadota Shin 信州大学, 学術研究院医学系, 助教 (70799064)
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 成熟心筋 / 多能性幹細胞 / 心筋成熟化 |
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| Outline of Final Research Achievements |
To elucidate the mechanisms of maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), we established a reporter hPSC line to detect and select matured cardiomyocytes by CRISPR/ Cas9 gene-editing. We have succeeded in the establishment of the reporter cell line, however, the fluorescent signal was too weak to detect the matured cardiomyocytes, therefore we need to modify the gene-editing strategy. We did also in vivo transplantation study which compared one-month cultured hPSC-CMs with two-month cultured hPSC-CMs. Although hPSC-CMs matured in a time-dependent manner in vivo, an extended in vitro culture period appeared to enhance maturation of hPSC-CMs after transplantation.
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| Academic Significance and Societal Importance of the Research Achievements |
多能性幹細胞（ES/iPS細胞）は、多分化能と無限の増殖能をもった細胞であり、再生医療のみならず、創薬、病態解明のツールとして研究開発が進んでいる。ただし、1つの問題点として、これまで報告された分化心筋細胞は、胎児型心筋と同様に未熟である。様々な方法で成熟化を促進すると報告されているが、ヒト多能性幹細胞由来心筋細胞で成人型と全く同様に成熟させた報告はこれまでにない。特に、再生医療への応用において、サルなどの大動物へ移植後に一過性の心室性不整脈が出現することが報告され、その原因の一つが移植心筋細胞の未熟性によると考えられるため、心筋成熟化は極めて重要な課題である。
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