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

细胞因子对电离辐射照射下人CD34+造血干细胞细胞修复系统的功能分析

• 批准号: 23791382
• 负责人: MONZEN Satoru
• 金额: $ 2.75万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791382/
• 关键词: 造血幹細胞; 放射線障害; サイトカイン; 細胞修復; 骨髄系造血前駆細胞; 電離放射線; 細胞増殖; 細胞表面抗原; 巨核球・血小板造血

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

造血干/祖细胞暴露于电离辐射导致以线性能量转移和/或剂量依赖性方式显著抑制成熟功能性血细胞的产生。为了表征不同类型的线性能量转移辐射在细胞因子刺激下对人骨髓造血的影响，在体外比较了暴露于碳离子束或X射线的人CD 34 ^+细胞的造血。培养基包括适当的细胞因子组合（TPO、IL-3、SCF、EPO、G-CSF和GM-CSF）。暴露于碳离子束的总髓系祖细胞的存活分数显著低于暴露于X射线的细胞，表明这些细胞对碳离子束比X射线的情况更敏感。在粒细胞-巨噬细胞和红系祖细胞中分别观察到类似的敏感性。在液体培养14天后，单个核细胞总数无显著差异， ...更多信息 在未照射的对照培养物和暴露于0.5戈伊X射线的细胞之间，而0.5戈伊碳离子束抑制细胞增殖至对照的4.9%，与暴露于1.5戈伊X射线的细胞的水平相似。与终末成熟相关的细胞表面抗原，如CD 13、CD 14和CD 15，在从X射线暴露的细胞培养物中收获时几乎与来自非辐照对照培养物的那些相同。X射线增加了CD 235 ^+红细胞相关的分数，而碳离子束增加了CD 34 ^+ CD 38 ^-原始细胞分数和CD 13 ^+ CD 14 ^+/-CD 15 ^-分数。在CD4^1+ CD 45 ^+巨核细胞部分中，尽管与未照射对照相比该部分没有显著差异，但早期造血相关基因FLI 1、HOXB 4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HO 1和NQO 1在第7天上调。这些结果表明，尽管不同类型的辐射对HSPCs来源的成熟髓系细胞表面抗原表达的影响与对照组相似，但碳离子束对髓系造血祖细胞的克隆生长造成了严重的损伤。少

项目成果

Effects of Ionizing Radiation on Proliferation and Differentiation of Mouse Induced Pluripotent Stem Cells

• DOI: 10.1269/jrr.11138
• 发表时间: 2012-03-01
• 期刊: JOURNAL OF RADIATION RESEARCH
• 影响因子: 2
• 作者: Hayashi, Naoki;Monzen, Satoru;Kashiwakura, Ikuo
• 通讯作者: Kashiwakura, Ikuo

Terminal Maturation of Megakaryocytes and Platelet Production by Hematopoietic Stem Cells Irradiated with Heavy-Ion Beams

• DOI: 10.1667/rr2392.1
• 发表时间: 2011-07-01
• 期刊: RADIATION RESEARCH
• 影响因子: 3.4
• 作者: Monzen, Satoru;Takahashi, Kenji;Kashiwakura, Ikuo
• 通讯作者: Kashiwakura, Ikuo

Effects of radiation on the maturation of megakaryocytes.

• DOI: 10.1093/jrr/rrs127
• 发表时间: 2013-05
• 期刊: Journal of radiation research
• 影响因子: 2
• 作者: Hirose K;Monzen S;Yoshino H;Sato H;Aoki M;Hatayama Y;Kawaguchi H;Sato M;Narita Y;Takai Y;Kashiwakura I
• 通讯作者: Kashiwakura I

放射線分割曝露がヒト造血幹細胞からの骨髄系分化に与える影響

分段辐射暴露对人造血干细胞骨髓分化的影响

• 发表时间: 2012
• 作者: Monzen S;Takahashi K;Yoshino H;Kasai-Eguchi K;Kashiwakura I.;門前暁,木下智子,柏倉幾郎
• 通讯作者: 門前暁,木下智子,柏倉幾郎

Radioprotective effects of (-)-epigallocatechin-3-gallate on human erythrocyte/granulocyte lineages.

(-)-表没食子儿茶素-3-没食子酸酯对人红细胞/粒细胞谱系的辐射防护作用。

• DOI: 10.1093/rpd/ncs226
• 发表时间: 2012
• 期刊: Radiation Protection Dosimetry
• 影响因子: 1
• 作者: Monzen S;Kashiwakura I.
• 通讯作者: Kashiwakura I.