Recombinant rat stem cell factor synergizes with recombinant human granulocyte colony-stimulating factor in vivo in mice to mobilize peripheral blood progenitor cells that have enhanced repopulating potential

Abstract

Splenectomized mice treated for 7 days with pegylated recombinant rat stem cell factor (rrSCF-PEG) showed a dose-dependent increase in peripheral blood progenitor cells (PBPC) that have enhanced in vivo repopulating potential. A dose of rrSCF-PEG at 25 micrograms/kg/d for 7 days produced no significant increase in PBPC. However, when this dose of rrSCF-PEG was combined with an optimal dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 200 micrograms/kg/d), a synergistic increase in PBPC was observed. Compared with treatment with rhG-CSF alone, the combination of rrSCF-PEG plus rhG-CSF resulted in a synergistic increase in peripheral white blood cells, in the incidence and absolute numbers of PBPC, and in the incidence and absolute numbers of circulating cells with in vivo repopulating potential. These data suggest that low doses of SCF, which would have minimal, if any, effects in vivo, can synergize with optimal doses of rhG-CSF to enhance the mobilization of PBPC stimulated by rhG-CSF alone.

Transplantation of Allogeneic Peripheral Blood Stem Cells Mobilized by Recombinant Human Granulocyte Colony Stimulating Factor

“…However, there are no published reports describing the use of non-syngeneic donors in the mouse model to evaluate graft rejection or GVHD. In murine models, stem cell factor (SCF) and G-CSF or a combination of the two increases the concentration of colony forming units-spleen (CFU-S) in the peripheral blood [32][33][34][35][36][37]. In the mouse, IL-8 also mobilizes PBSC which have long-term marrow repopulating ability [38].…”

The role of stem cell factor in mobilization of peripheral blood progenitor cells: Synergy with G‐CSF

“…In recent studies, we have examined the role of pegylated recombinant rat stem cell factor (rrSCF-PEG) alone and in combination with rhG-CSF in mobilization of PBPC with the ability of rescuing lethally irradiated mice [40]. Based upon previous studies by Dexter and colleagues [41], splenectomized mice were treated daily for seven days with growth factors given by intravenous injection.…”

On how Rac controls hematopoietic stem cell activity

“…While marrow harvests were previously used to collect transplantable HSCs, current clinical practice mostly applies the biological phenomenon of HSC/P mobilization from the marrow into the PB which allows leukoapheresis harvest, 9 as this does not require general anesthesia and is typically associated with shorter periods of postpancytopenia. 7,10 Administration of cytokines, such as granulocytecolony stimulating factor (G-CSF) 2 or stem cell factor (SCF), 11 chemokine-receptor inhibitors (e.g., AMD3100), 12 and cytotoxic drugs (e.g., cyclophosphamide) [2][3][4][5][6] have been used clinically to increase the number of circulating HSC/P. A goal of PB stem cell transplant (PBSCT) for hemato-oncological diseases is to optimize the number of HSCs to ensure low levels of the morbidity and mortality that is associated with rescue in the myeloablative setting.…”