2023 Fiscal Year Final Research Report
Regeneration of vascular endothelial function in pulmonary hypertension by ex vivo amplified and cultured vascular endothelial progenitor cells
| Project/Area Number |
21K08166
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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 53030:Respiratory medicine-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田中 里佳 順天堂大学, 医学部, 教授 (70509827)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 肺動脈性肺高血圧症 / 生体外増幅培養 / 末梢血単核球 / マクロファージ / 血管内皮前駆細胞 / 細胞移植 |
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| Outline of Final Research Achievements |
Intravascular administration of ex vivo amplified cultured peripheral blood mononuclear cells (MNC-QQc) improved pulmonary circulation and vascular remodeling in pulmonary arterial hypertension (PAH) rats. MNC-QQc from donors settled in the lung tissue stroma of recipient PAH rats, mostly M2 macrophages. Furthermore, removal of M2 macrophages from MNC-QQc abolished the PAH ameliorating effect. Comprehensive genetic analysis of whole lung tissue revealed that MNC-QQc suppressed the expression of inflammation-related genes, especially TACR-1 gene expression was suppressed by M2 macrophages. TACR-1 is expressed on the neurokinin-1 receptor (NK-1R), which triggers inflammation. These results suggest that MNC-QQc may contribute to the control of PAH progression via suppressing NK-1R related inflammation.
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| Free Research Field |
肺循環障害
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| Academic Significance and Societal Importance of the Research Achievements |
各種肺血管拡張薬の開発によってPAHの予後は劇的に改善したが、強い血管内皮細胞障害と血管リモデリングを有する治療抵抗性の重症PAHでは、肺移植以外に有効な治療手段がないのが現状である。本研究では、単発のMNC-QQc投与でPAHラットの肺循環動態に加えて肺動脈リモデリングが改善しており、肺血管拡張薬にはない抗リモデリング効果を有する新規治療としても期待される。細胞移植という、これまでにない発想のPAH治療コンセプトであり、特に重症例に対する治療戦略を大きく変える可能性を含む研究成果と考えている。
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