THYMIC TRANSPLANTATION OF STEM CELLS

尽管开发了新的免疫抑制药物， 慢性和急性排斥反应仍然是患者的重要原因 人体实体器官的发病率、器官衰竭和死亡 移植。该项目的目标是确定是否 将供体干细胞注入胸腺可导致(1)干细胞 细胞植入与持续性外周血微嵌合体 (供体细胞在受者血液中共存而不会导致 接收者免疫攻击)和(2)修改接收者的 免疫系统与移植物存活时间的关系 干细胞捐献者。这些研究的最终目的是 开发一种诱导对固体器官的耐受性(接受)的方法 在不使用终身免疫抑制药物的情况下移植。在……里面 前些年我们发现胸腺内干细胞移植可以 导致供体来源的细胞长期存活，这 导致皮肤移植接受度延长。我们目前正在 评价不同亚型骨髓的特性 干细胞来确定哪些细胞群最适合胸腺内 移植和实现微嵌合体。这是由以下人员完成的 (1)通过细胞表面评价干细胞亚型的体外实验 标记和功能特性以及(2)活体实验， 将不同群体的干细胞移植到实验动物体内 动物和监测微嵌合体的发展。结果 在过去一年中获得的结果表明，骨髓来源的干细胞 细胞的异质性很强，而且所用细胞的特定类型 胸腺内移植可能是这一成功的关键 修改受体免疫系统的方法。未来的研究将 评价干细胞移植和微嵌合体的效果 接受实心器官(心脏)移植。这些研究是 在灵长类动物身上表演是因为这些动物提供了最多 在对该方法进行测试之前，对其进行改进的直接模型 移植病人。

In spite of the development of new immunosuppressive drugs, chronic and acute rejection remains a significant cause of patient morbidity, organ failure, and death in human solid organ transplantation. The goal of this project is to determine whether injection of donor stem cells into the thymus can result in (1) stem cell engraftment and persistent peripheral blood microchimerism (coexistence of donor cells in recipient blood without inducing a recipient immune attack) and (2) modification of the recipient's immune system and prolonged graft survival of solid organ grafts from the stem cell donor. The ultimate objective of these studies is to develop a method of inducing tolerance (acceptance) of a solid organ graft without the use of life-long immunosuppressive drugs. In previous years we showed that intrathymic stem cell implantation could result in long-term survival of donor-derived cells and that this resulted in prolonged skin graft acceptance. We are currently evaluating the characteristics of various sub-types of bone marrow stem cells to determine which populations are "best" for intrathymic transplantation and achieving microchimerism. This is being done by (1) in vitro assays evaluating stem cell sub-types by cell surface markers and functional characteristics and (2) in vivo experiments, transplanting different populations of stem cells into experimental animals and monitoring development of microchimerism. Results obtained during the past year suggest that bone marrow-derived stem cells are very heterogeneous, and that the specific type of cell used for intrathymic transplantation may be critical to the success of this method of modifying the recipient immune system. Future studies will evaluate the effects of stem cell transplantation and microchimerism on the acceptance of a solid organ (heart) graft. These studies are being performed in primates because these animals provide the most direct model for refining this method before it is tested in transplant patients.