THYMIC TRANSPLANTATION OF STEM CELLS

干细胞胸腺移植

• 批准号: 6277603
• 负责人: MARGARET D ALLEN
• 金额: $ 7.23万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277603
• 关键词: Mammalia; Primates; animal tissue; cardiovascular system; hematology; skin; transplantation

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.

尽管开发了新的免疫抑制药物，但 慢性和急性排斥仍然是患者的重要原因 人类固体器官中的发病率，器官衰竭和死亡 移植。 该项目的目的是确定是否 将供体干细胞注入胸腺可能导致（1）茎 细胞植入和持续的外周血微chimerismism （受体血液中供体细胞共存而不诱导A 接受者免疫攻击）和（2）修改接收者 免疫系统和固体器官移植物的延长移植物存活 干细胞供体。 这些研究的最终目标是 开发一种诱导固体器官耐受性（接受）的方法 不使用终身免疫抑制药物的移植物。 在 前几年，我们表明胸膜干细胞植入可能 导致供体衍生细胞的长期生存，这 导致了长时间的皮肤接枝接受。 我们目前 评估骨髓各种子类型的特征 干细胞确定哪些人群对于胸膜 移植和实现微思维主义。 这是由 （1）通过细胞表面评估干细胞亚型评估干细胞亚型的体外测定 标记和功能特征以及（2）体内实验， 将不同种群的干细胞种群移植到实验中 动物和监测微智力的发展。 结果 在过去的一年中获得的表明骨髓衍生的茎 细胞非常异质，并且使用的特定类型使用 对于内加性移植可能对这一成功至关重要 修改受体免疫系统的方法。 未来的研究将 评估干细胞移植和微chimerismism的影响 关于接受固体器官（心脏）移植物的接受。 这些研究是 由于这些动物提供的最多，因此在灵长类动物中表演 在对此方法进行测试之前，用于完善此方法的直接模型 移植患者。