IN-UTERO TRANSPLANTATION OF HUMAN FETAL HEMATOPOIETIC-CELLS IN NOD SCID MICE/

We have previously demonstrated that high levels of allogeneic, donor- derived mouse haemopoietic progenitor cells engraft following in utero transplantation in NOD/SCID mice. To evaluate whether the fetal NOD/S CID haemopoietic microenvironment supports the growth and development of human fetal haemopoietic progenitor cells, we injected fetal liver mononuclear cells (FL) or fetal bone marrow (FBM) derived CD34(+) cell s into NOD/SCID mice on day 13/14 of gestation. At 8 weeks of age 12% of FBM recipients and 10% of FL recipients were found to have been suc cessfully engrafted with CD45(+) human cells. CD45(+) cells were prese nt in the BM of all chimaeric animals; 5/6 recipients showed engraftme nt of the spleen, and 4/6 recipients had circulating human cells in th e peripheral blood (PB). The highest levels of donor cells were found in the BM, with up to 15% of the nucleated cells expressing human spec ific antigens. Multilineage human haemopoietic engraftment, including B cells (CD19), myelomonocytic cells (CD13/33) and haemopoietic progen itor cells (CD34), was detected in the BM of chimaeric mice. In contra st, no human CD3(+) cells were detected in any of the tissues evaluate d. When the absolute number of engrafted human cells in the PB, BM and spleens of chimaeric mice was determined, a mean 16-fold expansion of human donor cells was observed. Although multilineage engraftment occ urs in these fetal recipients, both the frequency and the levels of en graftment are lower than those previously reported when human cells ar e transplanted into adult NOD/SCID recipients.