2019 Fiscal Year Final Research Report
Establishment of efficacy and safety for the treatment of severe heart failure using human induced pluripotent stem cells
| Project/Area Number |
18K15903
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | 再生医療 / iPS細胞 / 重症心不全 / 心筋細胞移植 / 催不整脈 |
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| Outline of Final Research Achievements |
When purified human iPS cell-derived cardiomyocytes (hiPSC-CMs) were transplanted to the hearts of immunodeficient mice and rats as cardiac spheroids, the recipient-derived angiogenesis was observed in the transplanted cells, and a large amount of hiPSC-CMs were engrafted. No teratoma formation was observed. The transplanted hiPSC-CMs expressed connexin 43, which indicated they could form gap junctions for electrophysiological activity. On the other hand, tumor formation was confirmed in the non-purified hiPSC-CMs group. From these results, it was confirmed that the metabolic purification enables the safe long-term engraftment of hiPSC-CMs. Further, the improvement of cardiac function was clarified by transplantation to heart failure model of rats. It was pathologically confirmed that the hiPSC-CMs have more mature sarcomere. Moreover, effectiveness and arrhythmogenicity were evaluated by transplanting hiPSC-CMs to the ischemia-reperfusion model of monkeys.
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| Free Research Field |
循環器内科
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトiPS細胞由来の心筋細胞は未熟な心筋細胞であり、分化誘導後には非心筋細胞が多く含有されている。未精製あるいは純化精製後の心筋細胞が移植後長期経過観察後に腫瘍化するかどうかは明らかではなかった。本研究の成果によって、ヒトiPS細胞由来心筋細胞は移植後に長期生着し機能することが明らかになった。また、造腫瘍性と催不整脈の有無も評価しており本研究によってヒトiPS細胞由来心筋細胞の安全性と有効性が確認される。今後の臨床応用にむけて社会的インパクトは非常に大きい。今後はヒトへの臨床応用によって再生心筋細胞を用いた心不全治療が重症心不全患者の希望となることが期待される。
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