| Project/Area Number |
17K10135
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kanazawa University (2018-2019)
Department of Clinical Research, National Hospital Organization Kanazawa Medical Center (2017) |
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Principal Investigator |
HIDEAKI MAEBA 金沢大学, 附属病院, 特任助教 (10419335)
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| Co-Investigator(Kenkyū-buntansha) |
西村 良成 金沢大学, 附属病院, 講師 (50324116)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | GVHD / psoralen / UVA / 制御性樹状細胞 |
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| Outline of Final Research Achievements |
We have reported that bone marrow-derived dendritic cells (BM-DCs), which are generated from bone marrow cells plus GM-CSF, acquired tolerogenicity by PUVA-treatment(psoralen+UVA 2J/cm2) in mice.The PUVA-treated DCs have tolerogenic function in a MHC-independent manner. But these cells did not have the inhibitory effects in the mouse GVHD model. We tried to improve the manufacture condition of PUVA-DC, to make these cells engraft effectively in vivo. At first, we researched the setting (0-2 J /cm2) of the UVA radiation, but did not have acquired tolerance in the UVA 0.2-1J/cm2 setting. Next, we added caspase inhibitor to PUVA treatment for apoptotic suppression by the UVA radiation. The survival rate 24 hours after PUVA-treatment were not improved, and these cells did not have the acquired more tolerance than conventional PUVA-DC. The examination of the further culture condition is necessary to use PUVA-DC for cell therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
造血幹細胞移植の合併症であるGVHDはHLA適合や免疫抑制剤の開発がなされてきた現在においてもII度以上のGVHDは非血縁者間で40%以上発症し、原疾患の治癒が得られても死亡する症例が存在する。
我々は、マウス骨髄細胞からpsolarenと紫外線(UVA)を用いて、制御性樹状細胞（PUVA-DC）を開発し、その細胞はマウスモデルでMHC非依存性にTリンパ球に対し抑制性の作用を示した。この技術を人に応用し、HLAの壁を乗り越える安全な骨髄移植開発のため、PUVA-DCの至適作製条件の検討を行った．
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