THYMIC TRANSPLANTATION OF STEM CELLS

这项提议的目的是在灵长类动物中测试一种新的方法， 产生对供体CD 34+移植物的耐受性 移植到受体胸腺 在试点研究中，我们实现了 1)狒狒的外周血微嵌合体 免疫抑制; 2）供体与第三方的特异性延长 皮肤移植物存活; 3）14岁时无移植物抗宿主病 个月 我们现在正在检验这一点的有效性和可行性 方法在幼年狒狒模型作为临床前试验。 在 在过去的一年里，我们发现选择的CD 34+细胞亚群比 在混合淋巴细胞培养物中同种异体刺激，因此可能更多 有望成为耐受原。 这些干细胞亚组分 外周血微嵌合体（供体细胞在受体中循环 血液）比全干细胞更可靠和更持久 制剂，也有希望用于致耐受性功能。 最后在 狒狒在胸腺内注射 干细胞亚组分，三种心脏移植物之一的存活率 延长到对照移植物存活时间的两倍以上。 未显示存活延长的移植物是在 被干细胞注射致敏。 我们现在 研究短暂性免疫抑制的作用， 干细胞移植是为了解决 致敏 资助NIH赠款RR 00166和AI 37747。 艾伦，医学博士， Weyhrich，J.，Akimoto，H.，高尔湖，Hall，J.，Dalesandro，J.，赛 美国，托马斯，R.，纳尔逊，K.A.，Andrews，R.G.长期同种异体 异种微嵌合体可以在不匹配的灵长类动物中实现 通过胸腺内直接植入CD 34+而不进行免疫抑制 捐献骨髓细胞 Cell. Immunol.181：127-138，1998. 艾伦，医学博士， Gaur，L.K.，纳尔逊，K.，de Fries，R.，Delio，P.，Anasetti角，和 Andrews，R.G.微嵌合体在不相关的灵长类动物中诱导， 未成熟的CD 34+供体干细胞的免疫抑制。 摘要第十届会议 国际大会免疫学，1998年11月，印度，新德里。

The aim of this proposal is to test in primates a new method for producing tolerance to solid organ grafts implantation of donor CD34+ stem cells into the recipient thymus. In pilot studies, we achieved 1) peripheral blood microchimerism in baboons with or without immunosuppression; 2) specific prolongation of donor vs. third-party skin graft survival; and 3) absence of graft vs. host disease at 14 months. We are now testing the validity and feasibility of this approach in a juvenile baboon model as a pre-clinical trial. In the past year, we found that selected subsets of CD34+ cells were less allostimulatory in mixed lymphocyte cultures, and thus might be more promising as tolerogens. These stem cell subfractions produced peripheral blood microchimerism (donor cells circulating in recipient blood) more reliably and more persistently than whole stem cell preparations, also promising for tolerogenic function. Finally, in baboons tested with cardiac grafts after intra th ymic injections of stem cell subfractions, the survival of one of three cardiac grafts was prolonged to more than twice the control graft survival time. Grafts that did not show prolongation of survival were in animals that became sensitized by the stem cell injection. We are now investigating the effect of transient immunosuppression at the time of stem cell implantation in order to obviate the problems of sensitization. FUNDING NIH grants RR00166 and AI37747. Allen, M.D., Weyhrich, J., Akimoto, H., Gaur, L., Hall, J., Dalesandro, J., Sai, S., Thomas, R., Nelson, K.A., and Andrews, R.G. Prolonged allogeneic and xenogeneic microchimerism can be achieved in unmatched primates without immunosuppression by direct intrathymic implantation of CD34+ donor marrow cells. Cell. Immunol. 181:127-138, 1998. Allen, M.D., Gaur, L.K., Nelson, K., de Fries, R., Delio, P., Anasetti, C., and Andrews, R.G. Microchimerism is induced in unrelated primates without immunosuppression by immature CD34+ donor stem cells. Abstr. 10th Intl Congr. Immunol., New Delhi, India, November 1998.