Characteristics of myeloid hematopoiesis derived from human hematopoietic stem cells exposed to ionizing radiation

Abstract

[Introduction] Hematopoietic stem cells (HSCs) are sensitive to extracellular oxidative stress. Exposure of the components of the hematopoietic system to ionizing radiation (IR) remarkably suppresses mature blood cell production in a LET- and/or a dose-dependent manner. However, information about how IR influences myeloid differentiation from HSCs is limited. This study investigated the effects of IR on myeloid hematopoiesis derived from human CD34⁺ cells exposed to heavy-ion beams and X-irradiation. [Methods] Human placental/umbilical cord blood CD34⁺ cells, which are HSCs, were separated using auto-MACS human CD34 selection kit (Miltenyi Biotech). Specific cell surface antigen expression was analyzed by direct immunofluorescence flow cytometry. Human CD34⁺ cells were exposed to monoenergetic carbon-ion beams (290 MeV/nucleon) and X-irradiation (150 kVp, 20 mA, 0.5 mmAl, and 0.3 mmCu filters). [Results and Conclusion] Total myeloid colony-forming cells (CFCs) among CD34⁺ cells exposed to heavy-ion beams, compared to those exposed CFCs among CD34⁺ cells exposed to X-irradiation, showed a significant decrease in D₀ and n, the parameters of radiosensitivity (heavy-ion beams: D₀ = 0.7 Gy, n = 1.1; X-irradiation: D₀ = 1.1 Gy, n = 1.9). On the stage of maturation, CD13⁺CD14^-/lowCD15⁺ neutrophil fraction derived from the X-irradiated CD34⁺ cells was significantly lower (7.7%) than that derived from non-irradiated control cells (22.2%). In addition, CD235a⁺ erythrocyte fraction increased to 64.1%, as compared to that derived from the non-irradiated control (41.9%). However, after heavy-ion beam irradiation, the amount of both these fractions was the same as that of the corresponding fractions derived from the control. These results suggest that the regeneration of myeloid hematopoiesis depends on LET and/or IR dose.