TRANSPLANTATION IN-UTERO OF FETAL HUMAN HEMATOPOIETIC STEM-CELLS INTOMICE RESULTS IN HEMATOPOIETIC CHIMERISM

Allogeneic and xenogeneic hematolymphoid chimerism has been achieved i n large and small animals using varied techniques to circumvent immune mediated graft rejection by the recipient. We show here the establish ment of long-term chimerism in normal mice transplanted in utero with human fetal hematopoietic stem cells (HSC). HSCs from fetal (13-20 wee ks' gestation) human livers were injected into fetal mouse peritoneal cavities on days 11-13 of gestation. Histologic examination demonstrat ed human chimerism in 29% of 38 live born mice using fluorescein conju gated antibodies to both the CD45 and CD14 antigens present on human p eripheral blood (PB) cells. Further investigation using flow cytometri c analysis of cells from 70 mice transplanted in utero revealed 28% of mice greater than 16 weeks of age contained human cells in at least o ne organ at the following frequencies: 14% PB, 8% bone marrow, 8% sple en and 12% thymus. These data indicate that human fetal HSC can be eng rafted into mouse fetuses. Additionally, the identification of circula ting human cells 18 months following transplantation supports the engr aftment and proliferation of a primitive hematopoietic progenitor.