2021 Fiscal Year Final Research Report
Cardiosphere-derived cells preconditioned lung macrophages to induce immune tolerance in the remote stressed heart
Project/Area Number |
19H03738
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 55030:Cardiovascular surgery-related
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Research Institution | Okayama University |
Principal Investigator |
Oh HIdemasa 岡山大学, 大学病院, 教授 (50372579)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 心臓内幹細胞 / 単心室 / マクロファージ / マイクロRNA / 肺高血圧症 |
Outline of Final Research Achievements |
Intravenously administered cardiosphere-derived cells (CDCs) engraft only transiently in recipient heart, but confer long-term therapeutic benefits in patients with heart failure. We demonstrated that intravenous injection of CDCs in single ventricle models preconditioned lung resident macrophages toward an immune regulatory phenotype in a Cx3cr1-dependent manner. The lung macrophage primed by lodged CDCs expressed high levels of miR-21, miR-221, and miR-217, and exhibited antifibrotic activities in volume loading heart. Adoptive transfer of either miRs prevented myocardial fibrosis and extended the life-span in the animal models of single ventricle; however, deletion of either of these miRs failed to attenuate the immune responses and inflammation in the stressed heart. Our results suggest that transplanted CDCs lodged in the lung may directly stimulate the endogenous macrophages within the engrafted lung to induce innate immune tolerance for functional recovery in the remote heart.
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Free Research Field |
循環器内科学
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Academic Significance and Societal Importance of the Research Achievements |
本研究により導かれた成果として、miR-21/miR/221/miR-217のin vivo導入することで、単心室ラットの生存予後の改善ならびに肺高血圧症による右心負荷がもたらす心室筋組織の線維化抑制に対して、細胞移植療法と同様の治癒効果があることを明らかにした。今後、次世代の細胞フリーの心筋組織修復法として、今後、単心室症症例に対する臨床研究の実施を目指し、基盤技術開発をさらに発展させていく。
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