Experimental research on the extremity alloeraft-Induction of immunotolerance and chimerism-

四肢同种异体移植物的实验研究-免疫耐受和嵌合的诱导-

• 批准号: 17591575
• 负责人: MURAMATSU Keiichi
• 金额: $ 2.24万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591575/
• 关键词: extremity allograft; immunotolerance; chimerism; FK506; GFP rat; LacZ rat

Recent advances in the field of transplant immunology and reconstructive surgery resulted in interest in extremity allograft. Until now, more than 20 hand transplants have been performed in human. Rejection is well controlled by currently available immunosuppressive drugs. The hand transplant, however, is not a life-supporting organ transplant and these drugs are unlikely to represent the final solution for hand transplantation due to serious adverse effects. The ultimate goal of extremity allograft is the induction of donor-specific immunotolerance. The major strategies for tolerance induction are: (1) T-cell co stimulation blockade, (2) induction of mixed chimerism (3), T-cell depletion, and (4) tolerance mediated by regulatory T-cells. Amongst these, the establishment of a high-level of chimerism may be the most stable strategy for donor-specific tolerance and our laboratory has been investigating the induction of macrochimerism following extremity allotransplantation. Recently, some studies demonstrated that macrochimerism induced immunotolerance for extremity allograft in the rodent model. We made a new protocol using cyclophosphamide (CYP) and granulocyte colony-stimulation factor (G-CSF) to induce high-level chimerism following rat whole-limb allotransplantation. Limb allografting could function as a vascularized carrier for bone marrow transplantation, provide a continuous source of donor cells and contribute to a high-level of chimerism in the recipient. Pre-transplant CYP followed by G-CSF and FK506 treatment significantly prolonged the survival of limb allografts but frequently caused chronic GVHD in the recipients

移植免疫学和重建手术领域的最新进展导致对肢体同种异体的兴趣。到目前为止，已经在人类中进行了20多次手术。当前可用的免疫抑制药物可以很好地控制拒绝。但是，手移植并不是生命支持器官的移植，这些药物不太可能代表由于严重的不良反应而导致的手部移植解决方案。肢体同种异体移植的最终目标是诱导供体特异性免疫耐受性。耐受性诱导的主要策略是：（1）T细胞CO刺激阻塞，（2）混合嵌合体（3），T细胞耗竭和（4）由调节T细胞介导的耐受性。其中，建立高级的嵌合可能是供体特异性宽容的最稳定策略，我们的实验室一直在研究末端同种异体移植后的宏观挑战。最近，一些研究表明，宏观核心在啮齿动物模型中诱导了同种异体的肢体耐受性。我们使用环磷酰胺（CYP）和粒细胞刺激因子（G-CSF）制定了一种新方案，以诱导大鼠全limb同种异体移植后诱导高级嵌合。肢体同种异体可以用作骨髓移植的血管化载体，提供供体细胞的连续来源，并有助于受体中高级的嵌合体。移植前CYP进行了G-CSF和FK506处理，显着延长了肢体同种异体移植的存活率，但经常引起受体的慢性GVHD

项目成果

Hand transplantation

• DOI: 10.1080/00016470510030283
• 发表时间: 2005-01
• 期刊: Acta Orthopaedica
• 影响因子: 3.7
• 作者: H. Kvernmo;V. Gorantla;Ruben Gonzalez;W. Breidenbach

Donor Cell Repopulation of Whole-limb Allografts in the Rat : Detection with Green Fluorescent Protein

大鼠全肢同种异体移植物的供体细胞再增殖：用绿色荧光蛋白检测

• 期刊: Plastic and Reconstructive Surgery (accepted)
• 作者: Muramatsu K;et al.;Muramatsu K et al.
• 通讯作者: Muramatsu K et al.

Prolonged survival of rat whole-limb allografts treated with cycl ophosphami de, granulocyte colony-stimulation factor and FK506.

用环磷酰胺、粒细胞集落刺激因子和 FK506 处理的大鼠全肢同种异体移植物的存活时间延长。

• 发表时间: 2006
• 期刊: Transpl Int 19(10)
• 作者: Muramatsu K;You-Xin S;Hashimoto T;Matsunaga T;Gondo T;Taguchi T.
• 通讯作者: Taguchi T.

ラット同種移植肢の細胞置換-GFPラットを用いた解析-

大鼠同种异体移植肢体的细胞置换 -使用 GFP 大鼠进行分析 -

• 发表时间: 2006
• 期刊: 日本マイクロサージャリー学会会誌 19・1
• 作者: Muramatsu K;You-Xin S;Hashimoto T;Matsunaga T;Taguchi T.;村松慶一 他
• 通讯作者: 村松慶一 他

The role of cyclophosphamide and granulocyte colony-stimulation factor in achieving high-level chimerism in allotransplanted limbs.

环磷酰胺和粒细胞集落刺激因子在同种异体移植肢体中实现高水平嵌合的作用。

• 发表时间: 2006
• 期刊: J Orthop Res. 24(11)
• 作者: Muramatsu K;et al.
• 通讯作者: et al.