INTRAUTERINE XENOTRANSPLANTATION OF FETAL BONE MARROW

胎儿骨髓宫内异种移植

• 批准号: 3329714
• 负责人: JOSEPH Alphonso BELLANTI
• 金额: $ 13.67万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3329714
• 关键词: DNA footprinting; Macaca mulatta; Primates; baboons; biological models; bone marrow transplantation; cytogenetics; embryo /fetus; embryonic stem cell; gestational age; hematopoietic tissue transplantation; karyotype; model design /development; tissue donors; tissue mosaicism; xenotransplantation

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.

本研究计划的总体目标是调查 胎儿免疫未成熟骨的宫内异种移植 来自一种非人类灵长类动物胎儿的骨髓干细胞 （恒河猴）到另一种非人类灵长类动物（狒狒）的胎儿。 这将通过检查一些细胞遗传学和 供体血液中造血系统的生化标志物 收件人的。 拟议的研究基于以下假设： 灵长类动物可以通过胎儿到胎儿实现造血嵌合 宫内移植，即使供体和受者均为同种异体 系统发育上不同的物种。 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，al 宫内异种移植后造血嵌合模型 将恒河猴胎儿骨髓干细胞移植到胎儿狒狒体内。 结果 这些研究的结果将与接受者的相对年龄相关 供体以及移植后嵌合的程度 受者处于出生后发育的各个阶段。 我们预计 通过这种造血和造血的纵向研究相结合的方法 免疫学重建，应该可以描绘出 控制胎儿异种移植的个体发生变量。 一个成功的 该研究成果将为该研究提供相关的动物模型 为几种人类先天性疾病制定异种移植策略 造血缺陷。