RECONSTITUTION OF SCID MICE WITH HUMAN LYMPHOID AND MYELOID CELLS AFTER TRANSPLANTATION WITH HUMAN FETAL BONE-MARROW WITHOUT THE REQUIREMENT FOR EXOGENOUS HUMAN CYTOKINES

Investigation of human hematopoietic maturation has been hampered by t he lack of in vivo models. Although engraftment of irradiated C.B-17 s cid/scid (SCID) mice with human progenitor cells occurred after infusi on with human pediatric bone marrow cells, significant engraftment of the mouse bone marrow with human cells was dependent upon continuous t reatment with exogenous human cytokines. Furthermore, despite cytokine treatment, only minimal peripheral engraftment of these mice with hum an cells was observed. In the present study, after infusion of irradia ted SCID mice with pre cultured human fetal bone marrow cells (BM-SCID -hu mice), their bone marrow became significantly engrafted with human precursor cells and their peripheral lymphoid compartment became popu lated with human B cells and monocytes independently of the administra tion of extraneous human cytokines. Examination of the bone marrow of the BM-SCID-hu mice for human cytokine mRNA gene expression demonstrat ed human leukemia inhibitory factor mRNA and interleukin 7 mRNA in nin e of nine BM-SCID-hu mice and macrophage-colony-stimulating factor mRN A in seven of eight BM-SCID-hu mice. This was an intriguing observatio n because these cytokines regulate different stages of human hematopoi esis. Since engraftment occurs in the absence of exogenous cytokine tr eatment, the BM-SCID-hu mouse model described should provide a useful in vivo system for studying factors important in the maturation of hum an myeloid and lymphoid cells in the bone marrow and the behavior of t he mature human cells after dissemination into the peripheral lymphoid tissue.