INTRAUTERINE XENOTRANSPLANTATION OF FETAL BONE MARROW

本研究提案的总体目标是调查 胎儿免疫未成熟骨宫内移植 一种非人类灵长类动物胎儿的骨髓干细胞 （恒河猴）与另一种非人类灵长类动物（狒狒）的胎儿。 这将通过检查几种细胞遗传学和 血液中供者造血系统的生化标志物 的接受者。 拟议的研究是基于这样的假设， 造血嵌合体可以在灵长类动物中通过胎儿到胎儿 子宫内移植，即使供体和受体 不同的物种。 平行调查线将 进行进一步发展正在进行的非人类灵长类动物实验， 宫内异种移植造血嵌合体模型的建立 恒河猴胚胎骨髓干细胞移植到狒狒胎儿体内。 结果 这些研究将与接受者的相对年龄相关， 供体以及移植后嵌合体的程度， 在出生后发育的各个阶段。 我们预计 通过这种联合的方法， 免疫重建，应该有可能描绘出 胚胎异种移植的个体遗传学变量。 一个成功 这项研究的结果将为研究提供一个相关的动物模型。 几种人类先天性心脏病的异种移植策略 造血缺陷

The overall goals of this research proposal are to investigate the intrauterine xenotransplantation of fetal immunologically immature bone marrow stem cells from the fetus of one species of non-human primate (rhesus) to the fetus of another species of non-human primate (baboon). This will be accomplished by examination of several cytogenetic and biochemical markers of the hematopoietic system of the donor in the blood of the recipient. The proposed research is based upon the hypothesis that hematopoietic chimerism can be achieved in primates by fetal to fetal intrauterine transplantation even when donor and recipient are of phylogenetically different species. Parallel lines of investigation will be conducted to further develop the ongoing nonhuman primate experiment, al model of hematopoietic chimerism following intrauterine xenotransplantation of rhesus fetal bone marrow stem cells into the fetal baboon. The results of these studies will be correlated with the relative ages of recipient and donor as well as with the degree of post-transplantation chimerism in the recipient at various stages of postnatal development. We anticipate that through this combined approach of longitudinal study of hematopoietic and immunologic reconstitution, it should be possible to delineate the ontogenetic variables governing fetal xenotransplantation. A successful outcome of this research will provide a relevant animal model for the development of xenotransplantation strategies for several human congenital hematopoietic defects.