| Project/Area Number |
17K10720
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
齋木 佳克 東北大学, 医学系研究科, 教授 (50372298)
川本 俊輔 東北大学, 医学系研究科, 非常勤講師 (20400244)
秋山 正年 東北大学, 医学系研究科, 准教授 (80526450)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 心筋炎 / Muse細胞 / 細胞治療 / 再生医療 / 再生医学 / 循環器・高血圧 |
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| Outline of Final Research Achievements |
Myocarditis is an inflammatory disease of cardiac tissue caused by different pathogens. Human bone marrow-derived Muse cells, human bone marrow-derived MSCs, and vehicle were intravenously injected 21 days later when myocarditis was most severe. Functional and histologic cardiac assessments at 2 weeks showed the preferential homing of Muse cells to the heart and spontaneous differentiation into cardiomyocytes and vascular cells. The left ventricular ejection fraction in the Muse group was significantly higher than that in vehicle and MSC groups. Muse cells also significantly suppressed myocardium apoptosis and fibrosis. Three-dimensional analysis of tissue-cleared samples demonstrated better vascular system reorganization in cardiac tissue of the Muse group.
Intravenously-injected Muse cells preferentially home to damaged cardiac tissue, replenish cardiomyocytes and vascular cells, and exert an improved by-stander effect compared to MSCs.
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| Academic Significance and Societal Importance of the Research Achievements |
心筋炎は未だ根本的治療法が確立されていない疾患である．本研究では心機能が最も低下するタイミングでのMuse細胞静脈投与により心機能改善効果が認められた．今後想定される臨床応用例として，重症心不全を呈した症例が挙げられる．特に，劇症型心筋炎のように心筋組織が廃絶した症例は，補助循環に依存して心臓移植を待つよりほかにない状態となる．重症心筋炎において急性期にMuse細胞治療を行うことでこのような症例の発生を未然に防ぐことが可能となれば，患者の生命予後の劇的な改善が期待でき，臨床的意義は極めて大きい．
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