Composite Tissue Transplantation

复合组织移植

• 批准号: 6623775
• 负责人: THOMAS H TUNG
• 金额: $ 10.19万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623775
• 关键词: CD40 molecule; T lymphocyte; artificial immunosuppression; biological models; enzyme linked immunosorbent assay; flow cytometry; histology; homologous transplantation; immune tolerance /unresponsiveness; immunocytochemistry; immunosuppressive; laboratory mouse; limb transplantation; mixed tissue /cell culture; transplant rejection; transplantation immunology

DESCRIPTION: The long-term goal of this proposal is to advance the clinical application of hand and composite tissue transplantation by reducing the adverse effects of immunosuppressive therapy. The role of composite tissue transplantation is based on functional and aesthetic reconstruction following trauma, congenital defect or cancer resection. The application of allogeneic reconstruction could avoid the limitations of donor-site morbidity and availability, and offer greater potential for the reconstruction of specialized structures such as limb and craniofacial components. A reliable murine model has been developed to study the immunology of composite tissue transplantation and to utilize recently available antibody therapies and genetically manipulated animals. Blockade of the CD40 costimulatory pathway is an important component of strategies that have been successful in prolonging the survival of skin and organ allografts in rodent and large animal models. This strategy has not been studied in a model of limb transplantation. The mechanism of action for the induction of immune unresponsiveness and the resistance to tolerance when used as a single agent in organ transplantation continues to be investigated. CD40 blockade appears to be most successful when combined with other therapies including donor bone marrow transfusion. The bone marrow component of a limb allograft distinguishes it from organ allografts, and may therefore have a greater potential for the induction of tolerance. The specific aims of this proposal are: 1) To determine the mechanism of resistance to limb allograft tolerance after treatment with CD40 blockade. 2) To develop a combined regimen for the induction of tolerance to limb allografts based on CD40 costimulation blockade. 3) To determine the mechanism of donor-specific immune unresponsiveness by a combined regimen based on CD40 blockade. Assessment techniques include mixed lymphocyte culture, flow cytometry, and the ELISPOT assay, in conjunction with histological and immunohistochemical assessment of allograft viability and rejection. The broad objective of this proposal is to improve the quality of reconstructive options and the quality of life for patients with devastating deformities.

产品说明： 该提案的长期目标是推进临床 应用手及复合组织移植， 免疫抑制治疗的副作用。复合组织的作用 移植基于功能和美学重建， 创伤、先天性缺陷或癌症切除术。同种异体移植的应用 重建可以避免供体部位发病率的限制， 可用性和 提供更大 潜力 重建 专门的结构，如肢体和颅面组件。 已经开发了一种可靠的小鼠模型来研究 复合组织移植和利用最近可用的抗体 疗法和 遗传操作 动物 封锁 的CD40 共刺激通路是已经被研究的策略的重要组成部分， 成功延长啮齿类动物皮肤和器官移植物的存活时间 和大型动物模型。这种策略还没有在肢体模型中研究过。 移植 诱导的作用机制 免疫 当作为单一药剂使用时， 在器官移植中的作用仍在研究中。 CD40阻滞出现 当与其他疗法结合时，包括供体骨， 骨髓移植 骨髓 分量 肢体 移植 将其与器官移植物区分开来，因此可能具有更大的 诱导耐受性的潜力。本提案的具体目标 主要有：1）探讨肢体移植耐受的抵抗机制 CD40阻断治疗后。 2)为了开发一种联合方案， 基于CD 40共刺激诱导同种异体肢体移植免疫耐受 封锁 第三章 以确定 的 机制 供者特异 免疫 基于CD40阻断的联合方案的无反应性。 评估 技术包括混合淋巴细胞培养、流式细胞术和ELISPOT 分析，结合组织学和免疫组织化学评估， 同种异体移植物存活和排斥。这项建议的主要目标是 提高重建选择的质量和生活质量， 严重畸形的病人