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2011
Conference Paper
Title
Modelling hematological parameters after irradiation in a stem cell transplantation model
Abstract
Introduction: The investigation of reconstitution in hematopoiesis after time- and dose-dependent irradiation in a model for hematological parameters is able to define the stem cell population and the resulting white blood cell population.
Materials and Methods: CD4-/- C57Bl/6 mice, transgenic for human CD4 and HLA-DR3, were irradiated in a single- (3, 6, 8 and 12 Gy) and fraction- (total 6, 9 and 12 Gy) dose regimen. Blood was analysed weekly for red blood cells (RBC), hemoglobin concentration (Hb), hematocrit (HCT) and white blood cells (WBC). Organ and tissue damage after irradiation was examined through histopathology.
Results: The recovery curves for RBC, Hb, HCT and WBC show the same velocity (< 1 week) for all doses but starting at different, dose-dependent times. The only dose-dependent parameter is defined by the beginning of the recovery process (dose-dependent shift). Furthermore, higher doses are related to a later recovery of the hematopoietic system. The RBC, Hb and HCT recovery is then followed by a saturation curve reaching a final concentration independent from the irradiation dose. Histological analysis of the bone marrow in the single dose cohort showed a dose-dependent reduction of the cellularity in the bone marrow cavities. The fractioned irradiation dose cohort resulted in a regeneration of all bone marrow cavities with a normal distribution of blood cells.
Conclusions: These findings might be of relevance in the refinement of strategies in the treatment of hematological malignancies and leads to a further understanding of the hematopoietic system after lethal irradiation.
Materials and Methods: CD4-/- C57Bl/6 mice, transgenic for human CD4 and HLA-DR3, were irradiated in a single- (3, 6, 8 and 12 Gy) and fraction- (total 6, 9 and 12 Gy) dose regimen. Blood was analysed weekly for red blood cells (RBC), hemoglobin concentration (Hb), hematocrit (HCT) and white blood cells (WBC). Organ and tissue damage after irradiation was examined through histopathology.
Results: The recovery curves for RBC, Hb, HCT and WBC show the same velocity (< 1 week) for all doses but starting at different, dose-dependent times. The only dose-dependent parameter is defined by the beginning of the recovery process (dose-dependent shift). Furthermore, higher doses are related to a later recovery of the hematopoietic system. The RBC, Hb and HCT recovery is then followed by a saturation curve reaching a final concentration independent from the irradiation dose. Histological analysis of the bone marrow in the single dose cohort showed a dose-dependent reduction of the cellularity in the bone marrow cavities. The fractioned irradiation dose cohort resulted in a regeneration of all bone marrow cavities with a normal distribution of blood cells.
Conclusions: These findings might be of relevance in the refinement of strategies in the treatment of hematological malignancies and leads to a further understanding of the hematopoietic system after lethal irradiation.
Conference