N Giri1, A Kaushiva, T Wu, S E Sellers, J F Tisdale. 1. Molecular and Clinical Hematology Branch, NIDDK, Hematology Branch, NHLBI, National Institutes of Health, Bethesda, MD, USA.
Abstract
OBJECTIVE: Previous studies have shown improved engraftment in a murine model when granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) were administered for 5 days prior to irradiation, with significant levels of engraftment in the growth factor-preconditioned group even at very low radiation doses. We sought to explore the mechanisms behind this effect. METHODS: The radiation sensitivity of mice with or without 5 days of prestimulation with G-CSF (200 microg/kg/d) and SCF (50 microg/kg/d) was compared. To further evaluate whether growth factor prestimulation enhances engraftment by mobilization of hematopoietic progenitors into peripheral blood, thus creating less endogenous competition within the marrow compartment, female mice were pretreated with 5 days of G-CSF/SCF or control diluent. Engraftment of 40 x 10(6) peripheral blood stem cells (PBSCs) harvested from G-CSF/SCF-mobilized male mice was compared in the two recipient groups. RESULTS: There was no difference in survival between the pretreated and control mice at the radiation doses tested. Additionally, there was no significant difference in the recovery of blood counts, bone marrow cellularity, colony-forming unit (CFU) content, or stem cell numbers assessed 4 months later in a competitive repopulation model. Engraftment levels of male cells did not differ between G-CSF/SCF-pretreated and control recipients, and could be detected in 30% of recipients at 20-24 weeks (4/12 in each group) at overall levels of 0.1-1%. CONCLUSIONS: The enhanced engraftment in cytokine pretreated recipients is unlikely to be due to increased endogenous stem-cell killing or to the creation of endogenous marrow "space" by egress of endogenous stem cells after cytokine prestimulation.
OBJECTIVE: Previous studies have shown improved engraftment in a murine model when granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) were administered for 5 days prior to irradiation, with significant levels of engraftment in the growth factor-preconditioned group even at very low radiation doses. We sought to explore the mechanisms behind this effect. METHODS: The radiation sensitivity of mice with or without 5 days of prestimulation with G-CSF (200 microg/kg/d) and SCF (50 microg/kg/d) was compared. To further evaluate whether growth factor prestimulation enhances engraftment by mobilization of hematopoietic progenitors into peripheral blood, thus creating less endogenous competition within the marrow compartment, female mice were pretreated with 5 days of G-CSF/SCF or control diluent. Engraftment of 40 x 10(6) peripheral blood stem cells (PBSCs) harvested from G-CSF/SCF-mobilized male mice was compared in the two recipient groups. RESULTS: There was no difference in survival between the pretreated and control mice at the radiation doses tested. Additionally, there was no significant difference in the recovery of blood counts, bone marrow cellularity, colony-forming unit (CFU) content, or stem cell numbers assessed 4 months later in a competitive repopulation model. Engraftment levels of male cells did not differ between G-CSF/SCF-pretreated and control recipients, and could be detected in 30% of recipients at 20-24 weeks (4/12 in each group) at overall levels of 0.1-1%. CONCLUSIONS: The enhanced engraftment in cytokine pretreated recipients is unlikely to be due to increased endogenous stem-cell killing or to the creation of endogenous marrow "space" by egress of endogenous stem cells after cytokine prestimulation.
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