ACQUIRED TOLERANCE TO CARDIAC XENOGRAFT

对心脏异种移植的获得性耐受

• 批准号: 2806173
• 负责人: Muhammad M Mohiuddin
• 金额: $ 1.34万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-11-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2806173
• 关键词: heart transplantation; immune tolerance /unresponsiveness; laboratory mouse; laboratory rat; transplantation immunology; xenotransplantation

Although clinical cardiac transplantation is effective therapy for patients with end stage cardiac disease the current shortage of donor organs limits the efficacy of this treatment. One solution to the organ donor shortage is the use of animal organs for human transplantation (xenotransplantation). Presently the immunologic barrier to xenotransplantation preclude this as a viable alternative. In previous work in an animal model of allo-transplantation, immune tolerance has been produced by exposure of the recipient animal to allogeneic cells either at a time when the immune system is immature (fetal, neonatal) or by exposing a transiently immunosuppressed mature animal to antigen intrathymicaIly. This research plan seeks to extend these observations to a model of xenotransplantation using a rat donor and mouse recipient. This model is advantageous since the availability of molecular reagents allows study of the mouse immune system at the molecular level. The research plan mirrors previous work in the allotransplant model. The research will explore different methods of exposing the immature murine immune system to rat cells and the subsequent response to a vascularizedcardiac graft. In addition, pretreatment of adult murine recipients will be followed by exposure to donor cells and subsequent vascularized cardiac xenotransplantation.

虽然临床上心脏移植是治疗 终末期心脏病患者目前供体短缺 器官限制了这种治疗的效果。器官的一个解决方案 供体短缺是使用动物器官进行人体移植 （异种移植）。目前的免疫屏障， 异种移植排除了这种可行替代方案。前几 在同种异体移植的动物模型中， 通过将受体动物暴露于同种异体细胞而产生 在免疫系统不成熟时（胎儿、新生儿）， 通过将暂时免疫抑制的成熟动物暴露于抗原 胸腺内注射这项研究计划旨在将这些观察结果扩展到 使用大鼠供体和小鼠受体的异种移植模型。 该模型是有利的，因为分子试剂的可用性 允许在分子水平上研究小鼠免疫系统。的 研究计划反映了以前在同种异体移植模型中的工作。的 研究将探索不同的方法， 免疫系统对大鼠细胞和随后的反应， 血管化心脏移植此外，成年小鼠的预处理 接受者随后将暴露于供体细胞， 血管化异种心脏移植