Analysis and clinical application of donor specific immunohyporesponsiveness using intraportal injection of myeloid dendritic cells in small bowel transplantation

门静脉注射髓系树突状细胞在小肠移植中供体特异性免疫低反应的分析及临床应用

• 批准号: 16591255
• 负责人: YAGI Takahito
• 金额: $ 2.24万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591255/
• 关键词: Small bowel transplantation; donor specific hyporesponsiveness; bone marrow transplantation; portal injection; dendritic cell; 拒絶反応; 骨髄細胞; グラフト潤滑リンパ球; サイトカインバランス; 骨髄由来樹状細胞

We have been reported that bone marrow cells were stronger effector cells than peripheral mononuclear cells in induction of donor specific hyporesponsiveness. And portal injection as administration route of donor antibody was more efficient than peripheral vessels with a small bowel transplantation (SBT) model. Even bone marrow transplantation (BMT) was given at the same time with the transplant surgery of SBT in the portal vein, induction efficiency didn't decrease, and the presensitization which obstructed transplantation was not caused. In order to increase the efficiency of the peculiar immune suppression acquisition by BMT with a rat SBT model, we planned bone marrow dendritic cell isolation, cultivation, maturation control and transplant experiments. It was confirmed that the main population of the induction of donor specific hyporesponsiveness was immature dendritic cell in the DAYO transportal BMT in SBT. And, though treatment by the immature dendritic cell significantly prolonged the graft survival of the rat SBT, it was found out that fatal GVHD was made to occur in BMT with the mature cell, and further examination could be necessary to the maintenance of a differentiation of cultured dendritic cell in the safer clinical application.

我们已经报道了骨髓细胞比外周单核细胞在诱导供体特异性低反应性方面更强的效应细胞。在小肠移植（SBT）模型中，门静脉注射作为供体抗体的给药途径比外周血管给药更有效。即使在门静脉SBT移植手术的同时进行骨髓移植，诱导效率也没有降低，也没有引起阻碍移植的现敏化。为了提高BMT在大鼠SBT模型上获得特异性免疫抑制的效率，我们计划了骨髓树突状细胞的分离、培养、成熟控制和移植实验。证实了SBT患者DAYO转运BMT中诱导供体特异性低反应的主要群体是未成熟树突状细胞。并且，虽然未成熟树突状细胞处理显著延长了大鼠SBT的移植物存活时间，但我们发现成熟细胞在BMT中会发生致死性GVHD，为了更安全的临床应用，需要进一步的研究来维持培养的树突状细胞的分化。

项目成果

The impact of portal infusion with donor-derived bone marrow cells and intracellular cytokine expression of graft-infiltrating lymphocytes on the graft survival in rat small bowel transplant model

门静脉输注供体骨髓细胞及移植物浸润淋巴细胞细胞内细胞因子表达对大鼠小肠移植模型移植物存活的影响

• 发表时间: 2004
• 期刊: Transplant Immunology 13
• 作者: Naoshi Mitsuoka;et al.
• 通讯作者: et al.

Prolonged survival of donor-specific rat intestinal allograft by administration of bone-marrow-derived immature dendritic cells.

• DOI: 10.1016/j.trim.2004.12.002
• 发表时间: 2005-03
• 期刊: Transplant immunology
• 影响因子: 1.5
• 作者: Dong Sheng Sun;H. Iwagaki;M. Ozaki;T. Ogino;S. Kusaka;Y. Fujimoto;H. Murata;H. Sadamori;H. Matsukawa;N. Tanaka;T. Yagi