| 研究実績の概要 |
In the original research proposal, the objective was to investigate the functional impact of induced trained immunity in aged hematopoietic stem cells (HSCs) and its role in the pathogenesis of clonal hematopoiesis of indeterminate potential (CHIP).
In the FY2023, significant progress was made towards this goal. Specifically, a highly specialized humanized mouse model was established, demonstrating robust engraftment of human hematopoietic stem cells (HSCs). These human cells not only populated the bone marrow but also migrated to peripheral blood and organs such as the spleen. To assess the potential for developing CHIP compatibility, we examined the development of xenograft tumors, both hematological and solid, in this mouse model, showed pronounced infiltration of human myeloid cells within the tumor microenvironment. Myeloid cells have been identified as key mediators 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 investigations are ongoing on inducing trained immunity in macrophages through treatment with immune modulatory reagents. These treatments are administered to CD34+ HSCs within aged-humanized mice, mimicking conditions reflective of human aging. Targeting macrophages, pivotal players in the immune response, is anticipated to yield deeper insights into immune training mechanisms.
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