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 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 x 10(6) 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.
van der Loo
J C
JC
Department of Pediatrics, Section of Hematology/Oncology, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indiana, IN, 46202, USA.
Hanenberg
H
H
Cooper
R J
RJ
Luo
F Y
FY
Lazaridis
E N
EN
Williams
D A
DA
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D002678:Chimera; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000494:pharmacology; D000069585:Filgrastim; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011994:Recombinant Proteins; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D019172:Transplantation Conditioning; D014183:Transplantation, Heterologous
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D000069585:Filgrastim