| Project/Area Number |
20K08400
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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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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Gifu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三上 敦 岐阜大学, 大学院医学系研究科, 特任教授 (60271524)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 心筋梗塞後心不全 / Muse細胞 / 心筋梗塞サイズ / 血管新生 / 不整脈 / 心筋再生 / 心機能改善 / 臨床応用 |
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| Outline of Research at the Start |
哺乳類の成体の心臓には、心筋梗塞などで障害を受けた後の再生能力がない。現在の急性心筋梗塞治療として、急性期の冠動脈形成術による冠動脈再灌流や各種薬剤による心臓リモデリング抑制、心機能保持が期待されますが、心機能低下例においては現存治療に限界があります。そこで我々は急性心筋梗塞治療に免疫応答に寛容で心筋への分化が期待できる間葉系由来のMultilineage-differentiating stress enduling cells ( Muse細胞 )を用いて心筋梗塞後心不全に対する心筋組織再生を目指すことを目的とした。
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| Outline of Final Research Achievements |
In a NIBS miniature pig (weighing approximately 15 kg), the middle part of the left coronary artery was ligated for 30 minutes under general anesthesia, and the left coronary artery was reperfused to create an acute myocardial infarction. On the day after surgery, the control group (n=10) received physiological saline, and the cell transplant group (n=10) received approximately 10 million GFP-labeled human Muse cells intravenously. Two weeks after reperfusion, blood tests and cardiac ultrasound were performed. Masson Trichrome staining confirmed myocardial infarct size, CD31 immunostaining confirmed angiogenesis, and Troponin I immunostaining confirmed engraftment and differentiation in myocardium.
The results showed that cardiac function was maintained better and tissue fibrosis was reduced in the Muse cell-administered group compared to the control group. We also confirmed the differentiation of Muse cells into cardiomyocytes and blood vessels.
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| Academic Significance and Societal Importance of the Research Achievements |
研究成果を論文で報告した。PloS One. 2022 Mar 24;17(3):e0265347.
ブタ心筋梗塞モデルでのMuse細胞治療はヒトへの応用の橋渡し的意義があり、今後の臨床応用への足掛かりとなり得る。但し、これまでの動物実験結果からは実際に投与されたヒトMuse細胞がブタ心筋にどの程度集積、分化したかは不明であった。その生着細胞数と有効な投与細胞数を検討するため、GFP標識ヒトMuse細胞移植でブタ心臓への生着細胞数と心機能改善への効果を検証することが求められる。
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