| Project/Area Number |
22K16302
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Kobe University |
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Principal Investigator |
Afroj Tania 神戸大学, 医学研究科, 学術研究員 (50913034)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Trained immunity / Humanized mouse model / Hematopoietic stem cell / aging / CHIP / Humanized mice / Hematopoietic stem cells / Aging / Clonal hematopoiesis / Xenograft model |
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| Outline of Research at the Start |
Hematopoiesis is considered as a life-long production house of immune cells and the integral component of trained immunity.
Notably, aging is coupled with functional derangements in immune cells and clonal hematopoiesis. The regulation of trained immunity in aging and clonal hematopoiesis (CHIP) is currently unknown. Here, I propose to uncover the regulatory mechanism of aging and CHIP pathogenesis by trained immunity, using humanized mouse models that are given several hematopoietic stress related to aging, hope to open a new dimension of “healthy aging”.
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| Outline of Final Research Achievements |
The original research proposal aimed to investigate the impact of induced trained immunity in aged HSCs and its role in CHIP pathogenesis.
To understand how human HSCs modulates the functions of its progeny populations in immune training in a relevant physiological condition, the generation of a humanized mouse model with robust engraftment of human HSCs that populated bone marrow, blood, and organs like the spleen. Xenograft tumor development in this model confirms CHIP compatibility, revealing significant human myeloid cell infiltration, key in transmitting trained immune responses from HSCs. Therefore,
the focus shifted towards elucidating the role of human myeloid cells, particularly macrophages derived from CD34+ HSCs, within this context. Current research aims to induce trained immunity in macrophages via immune modulatory treatments in aged-humanized mice, reflecting human aging. This is expected to provide deeper insights into immune training mechanisms.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト化マウスを用いた本研究により、病原体成分による老化造血幹細胞への刺激がヒト造血幹細胞自身に加えヒトマクロファージの機能にどのように影響を与えるか、訓練免疫の解明につながる成果が得られた。
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