| Project/Area Number |
17H06882
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Okayama University |
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Principal Investigator |
Asada Noboru 岡山大学, 大学病院, 助教 (70803055)
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| Research Collaborator |
MAEDA yoshinobu
MATSUOKA ken-ichi
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 造血幹細胞ニッチ / GVHD / 造血細胞ニッチ / 骨髄GVHD / 内科 |
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| Outline of Final Research Achievements |
An acute GVHD mice model was created using C3H/HeJ as a donor and either C57BL/6 or Nestin-GFP transgenic mice that can label perivascular niche cells as a recipient. Analysis of bone marrow at 21 days after transplantation indicates that the number of HSCs is significantly smaller in the allogeneic (allo) group than in the syngeneic (syn) group, suggesting that recovery of HSCs is impaired by the alloimmune response after transplantation. The number of perivascular niche cells were also significantly reduced in the allo group compared to the syn group. Moreover, the perivascular Nestin-GFP+ cells were also impaired the same as the GVHD model using wild-type mice. The decrease of niche cells was confirmed by analysis by both FACS and imaging. The present study revealed that the acute immune response after bone marrow transplantation also significantly damages perivascular niche cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、造血幹細胞ニッチとして注目されている血管周囲ニッチに着目し、さらには血管周囲ニッチを、動脈周囲ニッチと静脈周囲ニッチに分けて解析し、それぞれのニッチ細胞の役割を解明することに新規性がある。また、これまでのGVHD 治療は、免疫担当細胞をターゲットとしたものが中心であるが、本研究により、血管ニッチを照準とした新たな治療手段開発への糸口となることが期待される。さらに、骨髄GVHD の造血幹細胞ニッチ傷害のメカニズムが解明されれば、骨髄GVHD だけでなく再生不良性貧血などの、造血幹細胞ニッチをふくめた微小環境の異常に起因していると思われる、他の病態解明にも発展する可能性がある。
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