Improvement in making methods of PUVA-treated dendritic cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10135
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kanazawa University (2018-2019); Department of Clinical Research, National Hospital Organization Kanazawa Medical Center (2017)
• Principal Investigator: HIDEAKI MAEBA 金沢大学, 附属病院, 特任助教 (10419335)
• Co-Investigator(Kenkyū-buntansha): 西村 良成 金沢大学, 附属病院, 講師 (50324116)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: GVHD / psoralen / UVA / 制御性樹状細胞

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.

Free Research Field

小児血液

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．