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.
