Core--Microsurgery

显微外科手术。显微外科核心将为该计划的项目1、2和3提供动物移植模型的专业知识和质量控制。该核心单元将作为中心资源，利用耶鲁大学开发的免疫缺陷小鼠嵌合体中的人和猪动脉移植模型。双突变严重联合免疫缺陷(SCID)/米色小鼠被移植到人或猪的动脉上，随后通过过继转移人外周血单个核细胞(PBMC)进行免疫重建，和/或接受人或猪细胞因子治疗，如物种特异性T细胞衍生因子干扰素-γ(IFN-γ)。在一个替代性的人类实验模型中，白细胞或细胞因子与移植物血管细胞的相互作用导致免疫介导的动脉损伤。项目1将利用核心单元来测试假设，即非细胞溶解的干扰素-伽马分泌的T细胞可以在SCID/Beige小鼠中引起人动脉移植物动脉硬化(GA)。项目2将利用核心单位来确定干扰素-伽马在免疫缺陷小鼠宿主的人和猪动脉中引起GA的机制。项目3将利用核心单元来评估与产生干扰素-伽马的小鼠宿主反应的试剂的效用。项目3将利用核心单元来评估与产生干扰素-伽马的T细胞或与干扰素-伽马处理的血管细胞反应的试剂的用途，以检测免疫缺陷小鼠的人动脉移植物中的GA。项目3还可能使用小鼠异位心脏移植模型进行成像研究。显微外科核心的目标是：i)使用可靠的材料和技术向项目研究人员提供复杂的动物移植模型；ii)开发改进或适应体内模型的新方法；iii)为血管和移植生物学的研究人员提供协作的小动物显微外科培训资源。人PBMC-SCID/褐鼠动脉移植模型的方法学相对复杂，需要共享设施和特殊技能。显微外科核心人员对所需技术有广泛的了解，他们的综合专业知识对于确保模型的一致性和规模经济至关重要。通过向所有项目提供SCID/Beige小鼠宿主的动脉异种移植模型，显微外科核心将在该计划中发挥关键作用。

Microsurgery. The Microsurgery Core will provide expertise and quality control from animal transplantation models for Projects 1, 2, and 3 of the program. The core unit will serve as a central resource to utilize the human and pig artery transplantation models in immunodeficient mouse chimeras that have been developed at Yale University. Double-mutant severe combined immunodeficient (SCID)/beige mice are grafted with human or pig arteries and are subsequently immunologically reconstituted with an adoptive transfer of human peripheral blood mononuclear cells (PBMC) and/or are treated with human or pig cytokines, such as the species-specific, T cell-derived factor, interferon-gamma (IFN-gamma). The interactions of the leukocytes or cytokines with the graft vascular cells results in immune-mediated arterial injury in a surrogate human experimental model. Project 1 will utilize the core unit to test the hypothesis that non-cytolytic IFN-gamma-secreting T cells can cause graft arteriosclerosis (GA) of human arteries in SCID/beige mice. Project 2 will utilize the core unit to determine the mechanisms by which IFN- gamma causes GA in human and pig arteries in immunodeficient mouse hosts. Project 3 will utilize the core unit to evaluate the utility of reagents reactive with IFN-gamma-producing mouse hosts. Project 3 will utilize the core unit to evaluate the utility of reagents reactive with IFN-gamma- producing T cells or with IFN-gamma-treated vascular cells to detect GA in human artery grafts in immunodeficient mice. Project 3 may also use a murine heterotopic cardiac allograft model for imaging studies. The aims of the Microsurgery Core are: i) to provide the complex animal transplantation models to the program investigators using reliable materials and techniques; ii) to develop new methods for improving or adapting the in vivo models; and iii) to provide a collaborative small animal microsurgery training resource for investigators in vascular and transplantation biology. The methodology of the human PBMC- SCID/beige mouse artery transplantation model is relatively complex and requires shared facilities and special skills. The Microsurgery Core personnel have extensive with the required techniques and their combined expertise is essential to ensure consistency of the models and an economy of scale. By providing the artery xenograft model in SCID/beige mouse hosts to all of the projects, the Microsurgery Core will play a key role in this program.