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Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2556-2570
Nonobese Diabetic/Severe Combined Immunodeficiency (NOD/SCID)
Mouse as a Model System to Study the Engraftment and Mobilization
of Human Peripheral Blood Stem Cells
Johannes C.M. van der Loo,
Helmut Hanenberg,
Ryan J. Cooper,
F.-Y. Luo,
Emmanuel N. Lazaridis, and
David A. Williams
From the Department of Pediatrics, Section of Hematology/Oncology,
Herman B Wells Center for Pediatric Research, the Stem Cell Laboratory,
Cancer Research Building, and the Division of Biostatistics,
Regenstrief Institute for Health Care, Indiana University School of
Medicine, Indianapolis, IN; and Howard Hughes Medical Institute,
Indiana University School of Medicine, Indianapolis, IN.
Mobilized CD34+ cells from human peripheral blood (PB)
are increasingly used for hematopoietic stem-cell transplantation.
However, the mechanisms involved in the mobilization of human
hematopoietic stem and progenitor cells are largely unknown. To study
the mobilization of human progenitor cells in an experimental animal
model in response to different treatment regimens, we injected
intravenously a total of 92 immunodeficient nonobese diabetic/severe
combined immunodeficiency (NOD/SCID) mice with various numbers of
granulocyte colony-stimulating factor (G-CSF) -mobilized
CD34+ PB cells (ranging from 2 to 50 × 106
cells per animal). Engraftment of human cells was detectable for up to
6.5 months after transplantation and, depending on the number of cells
injected, reached as high as 96% in the bone marrow (BM), displaying
an organ-specific maturation pattern of T- and B-lymphoid and myeloid
cells. Among the different mobilization regimens tested, human
clonogenic cells could be mobilized from the BM into the PB (P
= .019) with a high 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 provide a basis to further study the mechanisms
of mobilization and the biology of the mobilized primitive human
hematopoietic cell.
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