NONOBESE DIABETIC SEVERE COMBINED IMMUNODEFICIENCY (NOD/SCID) MOUSE AS A MODEL SYSTEM TO STUDY THE ENGRAFTMENT AND MOBILIZATION OF HUMAN PERIPHERAL-BLOOD STEM-CELLS/

Mobilized CD34(+) cells from human peripheral blood (PB) are increasin gly used for hematopoietic stem-cell transplantation. However, the mec hanisms involved in the mobilization of human hematopoietic stem and p rogenitor cells are largely unknown, To study the mobilization of huma n progenitor cells in an experimental animal model in response to diff erent treatment regimens, we injected intravenously-a total of 92 immu nodeficient nonobese diabetic/severe combined immunodeficiency (NOD/SC ID) mice with various numbers of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34(+) PB cells (ranging from 2 to 50 x 10(6) cell s per animal). Engraftment of human cells was detectable for up to 6.5 months after transplantation and, depending on the number of cells in jected, reached as high as 96% in the bone marrow (BM), displaying an organ-specific maturation pattern of T- and B-lymphoid and myeloid cel ls. Among the different mobilization regimens tested, human clonogenic cells could be mobilized from the BM into the PB (P =.019) with a hig h or low dose of Human G-CSF, alone or in combination with human stem- cell factor (SCF), with an average increase of 4.6-fold over control, Therefore, xenotransplantation of human cells in NOD/SCID mice will pr ovide a basis to further study the mechanisms of mobilization and the biology of the mobilized primitive human hematopoietic cell. (C) 1998 by The American Society of Hematology.