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

将造血干细胞/祖细胞暴露于电离辐射下，以线性能量转移和/或剂量依赖的方式导致成熟功能血细胞产生明显抑制。为了研究细胞因子刺激下不同类型的线性能量传递辐射对人骨髓造血的影响，我们在体外比较了碳离子束和x射线对人CD34^+细胞造血的影响。培养基中加入适当的细胞因子组合（TPO、IL-3、SCF、EPO、G-CSF和GM-CSF）。总髓系祖细胞在碳离子束照射下的存活率明显低于x射线照射下的存活率，表明这些细胞对碳离子束的敏感性高于x射线照射下的敏感性。在粒细胞-巨噬细胞和红细胞祖细胞中分别观察到类似的敏感性。在液体培养中，未辐照对照培养和暴露于0.5 Gy x射线的细胞之间的单个核细胞总数没有显著差异，而0.5 Gy碳离子束对细胞增殖的抑制作用为对照的4.9%，与暴露于1.5Gy x射线的细胞的水平相似。与终端成熟相关的细胞表面抗原，如CD13、CD14和CD15，从x射线暴露的细胞培养中收获的细胞表面抗原与未照射的对照培养的细胞表面抗原几乎相同。x射线增加了CD235a^+红细胞相关部分，而碳离子束增加了CD34^+CD38^-原始细胞部分和CD13^+CD14^+/- cd15 ^-部分。在CD4^1+CD45^+巨核细胞部分中，尽管与未照射对照组相比，该部分没有显著差异，但早期造血相关基因FLI1、HOXB4和Tie-2，细胞因子受体基因KIT和IL-3RA，以及氧化应激相关基因HO1和NQO1在第7天上调。辐射暴露的这些反应可能直接或间接地通过细胞因子刺激参与细胞修复系统。这些结果表明，碳离子束对髓系造血祖细胞的克隆生长造成严重损害，尽管暴露于每种类型辐射的HSPCs衍生的成熟髓系细胞的细胞表面抗原表达与对照组相似。少

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