2018 Fiscal Year Final Research Report
Hematopoietic stem cell control by amino acids and development of novel therapeutic methods
| Project/Area Number |
16H02661
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山崎 聡 東京大学, 医科学研究所, 特任准教授 (50625580)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 造血幹細胞 / 骨髄ニッチ / アミノ酸 / バリン / BCAA / 骨髄移植 |
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| Outline of Final Research Achievements |
A specialized bone marrow microenvironment (niche) regulates hematopoietic stem cell (HSC) self-renewal and commitment. For successful donor-HSC engraftment, the niche must be emptied via myeloablative irradiation or chemotherapy. However, myeloablation can cause severe complications and even mortality. We found that the essential amino acid valine is indispensable for the proliferation and maintenance of HSCs. Both mouse and human HSCs failed to proliferate when cultured in valine-depleted conditions. In mice fed a valine-restricted diet, HSC frequency fell dramatically within 1 week. Furthermore, dietary valine restriction emptied the mouse bone marrow niche and afforded donor-HSC engraftment without chemoirradiative myeloablation. These project findings a critical role for valine in HSC maintenance and suggest that dietary valine restriction may reduce iatrogenic complications in HSC transplantation.
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| Free Research Field |
免疫学、血液学、免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
研究期間内に我々は，造血にアミノ酸のバランスが非常に重要であることが示された。これらの発見は今後の骨髄ニッチの機能および造血についてのさらなる研究が期待される。また，造血幹細胞と骨髄ニッチとの相互作用と同様の概念が白血病幹細胞においても提唱されていることから、バリンの欠乏した環境が造血幹細胞と同様に白血病細胞など悪性腫瘍においても効果が期待でき、アミノ酸の制御は移植の前処置やがんの分野においても新しい治療法となる可能性が示唆できることから、社会的な意義や波紋は大きかった。
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