2020 Fiscal Year Final Research Report
Study on the mechanism of HSC aging through quiescence maintaining culture
Project/Area Number |
19K17847
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | National Center for Global Health and Medicine |
Principal Investigator |
Kobayashi Hiroshi 国立研究開発法人国立国際医療研究センター, その他部局等, 研究員 (10749542)
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Project Period (FY) |
2019-04-01 – 2021-03-31
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Keywords | 造血幹細胞 / 静止期維持培養 / ステムセルエイジング |
Outline of Final Research Achievements |
Hematopoietic stem cells (HSCs) maintain lifelong hematopoiesis by remaining quiescent in the bone marrow niche. I recently developed a culture method to maintain HSCs quiescent in vitro. HSCs cultured in this system, however, exhibited aging-associated phenotype with the high level expression of CD41 and P-selectin. I improved the maintenance culture condition by searching for factors inhibiting and promoting CD41 and P-selectin expression in HSCs. Among various signal molecules, TGF-βand retinoic acid receptor signals promote the aging-associated phenotype, while cholesterol inhibited the aging phenotype. Thrombopoietn was inhibitory against CD41 expression at the range of low concentration, but was promoting at the higher range of concentration. Combining these factors, high TPO culture restored lymphopoiesis in old HSCs and resulted in higher reconstitution capacity than that of freshly isolated old HSCs.
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Free Research Field |
幹細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
造血幹細胞は幹細胞モデルとしての基礎科学的な側面と、造血幹細胞移植による血液疾患や先天性疾患の治療という臨床的な側面から重要な細胞である。しかし造血幹細胞の未分化性維持の必要最小限の要素は何か、そしてどのような環境因子が造血幹細胞を加齢させ、その機能喪失にかかわっているかは十分理解されておらず、結果として長期にわたる造血幹細胞の体外維持培養法も未確立であった。本研究により、幹細胞が生体内で一生涯にわたり維持されるメカニズムとは何か、そしてより良い移植医療のための質の高い幹細胞に必要な条件は何かという両面について、幹細胞の機能を維持する方法論を提供することにつながる。
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