The functional analysis of cell repair system by cytokines on humanCD34+ hematopoietic stem cells irradiated to ionizing radiation.

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Exposure of hematopoietic stem/progenitor cells to ionizing radiation causes a marked suppression of mature functional blood cell production in a linear energy transfer - and/or dose-dependent manner. With the aim of characterizing the effects of different types of linear energy transfer radiations on human myeloid hematopoiesis under the cytokine stimuli, hematopoiesis of human CD34^+ cells exposed to carbon-ion beams or X-rays was compared in vitro. The culture medium included appropriate cytokine combinations (TPO, IL-3, SCF, EPO, G-CSF and GM-CSF). The surviving fractions of total myeloid progenitors exposed to carbon-ion beams were significantly lower than those of cells exposed to X-rays, indicating that these cells are more sensitive to carbon-ion beams than the case of X-rays. Similar sensitivities were observed in granulocyte-macrophage and erythroid progenitors, respectively. In liquid culture for 14 days, no significant difference in total numbers of mononuclear cells was ob … More served between non-irradiated control culture and cells exposed to 0.5 Gy X-rays, whereas 0.5 Gy carbon-ion beams suppressed cell proliferation to 4.9% of the control, a level similar to that for cells exposed to 1.5Gy X-rays. Cell surface antigens associated with terminal maturation, such as CD13, CD14, and CD15, on harvest from the culture of X-ray-exposed cells were almost the same as those from the non-irradiated control culture. X-rays increased the CD235a^+ erythroid-related fraction, whereas carbon-ion beams increased the CD34^+CD38^- primitive cell fraction and the CD13^+CD14^+/-CD15^- fraction. In the CD4^1+CD45^+ megakaryocytes fraction, although there was no significant difference in this fraction in comparison to the non-irradiated control, the early hematopoiesis-related genes FLI1, HOXB4, and Tie-2, the cytokine receptor genes KIT and IL-3RA, and the oxidative stress-related genes HO1 and NQO1 were up-regulated on day 7. These responses by radiation exposure may be involved in cell repair system directly or indirectly by cytokine stimuli.These results suggest that carbon-ion beams inflict severe damage on the clonal growth of myeloid hematopoietic progenitors, although the expression of cell surface antigens by mature myeloid cells derived from HSPCs exposed to each type of radiation was similar to that by controls. Less