INTRAUTERINE XENOTRANSPLANTATION OF FETAL BONE MARROW

这项研究提案的总体目标是调查 胎儿免疫未成熟骨异种宫腔内移植 取自一种非人灵长类动物胎儿的骨髓干细胞 (恒河猴)传给另一种非人类灵长类动物(狒狒)的胎儿。 这将通过检查几个细胞遗传学和 献血者血液中造血系统生化标志物的研究 收件人的身份。拟议的研究是基于这样一个假设： 灵长类动物的造血嵌合体可以通过胎儿对胎儿的方式实现 宫内移植，即使供者和受者都是 在系统发育上不同的物种。平行的调查路线将 以进一步发展正在进行的非人类灵长类动物实验， 异种宫腔内移植后的造血细胞嵌合体模型 把恒河猴胎儿的骨髓干细胞移植到胎儿狒狒体内。结果是 这些研究将与接受者的相对年龄和 供者以及移植后嵌合体的程度 受者处于出生后发育的不同阶段。我们预料到 通过这一纵向研究的联合方法，对造血细胞和 免疫重建，应该有可能描绘出 控制胎儿异种移植的个体遗传学变量。一位成功的 本研究的结果将为下一步研究提供相关的动物模型。 几种人类先天性异种移植策略的研究进展 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.