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The study of therapy for radiation-induced thrombocytopenia by using ex vivo expanded-megakaryocyte prepared from auto hematopoietic stem cell.

The study of therapy for radiation-induced thrombocytopenia by using ex vivo expanded-megakaryocyte prepared from auto hematopoietic stem cell.
自体造血干细胞体外扩增巨核细胞治疗放射引起的血小板减少症的研究。
批准号:
15591253
负责人:
KASHIWAKURA Ikuo
金额:
$2.18万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2003
资助国家:
日本
项目状态:
已结题
起止时间:
2003 至 2005

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项目成果

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中文摘要
翻译
1.CD34抗原是一种新的人造血干细胞/祖细胞标记物。以CD34抗原表达为基础,从稳态人外周血(PB)中制备CD34^<低>和CD34^<高>两个细胞组分。CD34^<低>和CD34^<高>细胞组分中CD34^+CD45^+细胞的含量分别为74.8%和88.8%,血小板生成素(TPO)支持的集落形成单位巨核细胞(CFU-Meg)在CD34^<低>细胞组分中的出现频率是CD34^<高>细胞组分的1.9倍。CD34^<高>组的CFU-Meg比CD34^<低>组的CFU-Meg对辐射更敏感,表明稳态人PB中含有不同类型的CFU-Meg。TPO +白细胞介素-3是X射线照射后两种CFU-Meg存活的最佳组合。这些结果表明,与TPO的多种联合治疗将有助于放射后血小板减少症的细胞因子治疗。TPO诱导的PB CD34^+细胞培养的成熟巨核细胞具有较高的放射敏感性,但X照射后促血小板形成正常。这些结果表明,X射线照射对血栓形成结束的影响很小。低浓度的儿茶素-3-没食子酸酯(EGCg,100 nM)是一种主要的绿茶多酚,可以降低巨核细胞生成中辐射损伤的危险因素,提示EGCg在治疗血小板减少症方面的医学应用。CFU-Meg对碳离子束比x射线更敏感。碳离子束对CD34^+细胞DNA双链断裂(DSB)标志物γ-H2AX的诱导作用在细胞因子处理(如x射线)下没有增强。这些结果表明,细胞因子对CFU-Meg的DSB修复作用在碳离子束下比在x射线下更弱。IL-3与TPO的结合是x射线照射干细胞巨核细胞生成和血小板生成再生的最佳选择。我们的研究结果表明,通过适当的细胞因子组合刺激,x射线照射的干细胞可以诱导几乎正常的巨核细胞生成和血小板生成。少
英文摘要
1.CD34 antigen is a novel marker for human hematopoietic stem/progenitor cells. Two cell fractions, CD34^<low> and CD34^<high>, were prepared from steady-state human peripheral blood (PB) on the basis of CD34 antigen expression. The content of CD34^+CD45^+ cells in the CD34^<low> and CD34^<high> cell fractions was 74.8% and 88.8%, respectively, and the frequency of thrombopoietin (TPO)-supported colony-forming unit megakaryocytes (CFU-Meg) in the CD34^<low> cell fraction was 1.9 times higher than that in CD34^<high>. The CFU-Meg in CD34^<high> were more radiosensitive than those in CD34^<low>, indicating that steady-state human PB contains different types of CFU-Meg. TPO plus interleukin-3 was the optimal combination for survival of both types of CFU-Meg after X irradiation. These results suggest that multiple combinations with TPO will be helpful in cytokine therapy for post-irradiation thrombocytopenia.2.Mature megakaryocytes induced from the culture of PB CD34^+ cells with TPO are s … More hown high radio sensitivity, however, normal pro-platelet formation occurred after X irradiation. These results suggest that the influence of X irradiation to the end of thrombopoiesis is small.3.Low concentration of Epigallocatechin-3-gallate (EGCg,100 nM), a major green tea polyphenol, reduce the risk factor from radiation damage in megakaryocytopoiesis, suggesting the medical application of EGCg for the treatment of thrombocytopenia.4.CFU-Meg are more radiosensitive progenitors to cabon ion beam than X-ray. The induction of γ-H2AX, a marker of DNA double strand break (DSB), by carbon ion beam in CD34^+ cells was not enhanced by cytokine treatment such as that of X-ray. These results showed that the DSB repair of CFU-Meg by cytokine was lesser in progenitors to carbon ion beam than X-ray.5.A combination of IL-3 plus TPO would be an optimal choice for the regeneration of megakaryocytopoiesis and thrombopoiesis from X-irradiated stem cells. Our results suggest that nearly normal megakaryocytopoiesis and thrombopoiesis can be induced from X-irradiated stem cells by stimulation with appropriate cytokine combinations. Less
期刊论文(105)
专著(0)
科研奖励(0)
会议论文
Radiation sensitivity of hematopoietic stem/progenitor cells and cytokine action.
造血干/祖细胞的辐射敏感性和细胞因子作用。
DOI: --
发表时间: 2005
期刊: Jpn.J.Cancer Clin. 51(5)
影响因子: --
作者: [I.Kashiwakura et al., S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., T.Hamasu et al., I.Kashiwakura et al., D.Iizuka et al., 柏倉 幾郎, 柏倉 幾郎, S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., D.Iizuka et al., I.Kashiwakura et al.]
通讯作者: I.Kashiwakura et al.
A novel anticancer ribonucleoside, 1-(3-C-ethyl-β-D-ribo-pentofuranosyl) cytosine, enhances radidaion-induced cell death in tumor cells.
一种新型抗癌核糖核苷 1-(3-C-乙基-β-D-核糖-呋喃戊糖基) 胞嘧啶可增强肿瘤细胞中辐射诱导的细胞死亡。
DOI: --
发表时间: 2004
期刊: Radiat. Res. 162(6)
影响因子: --
作者: [I.Kashiwakura et al., S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., T.Hamasu et al., I.Kashiwakura et al., D.Iizuka et al., 柏倉 幾郎, 柏倉 幾郎, S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., D.Iizuka et al., I.Kashiwakura et al., I.Kashiwakura et al., I.Kashiwakura et al., T.Hamasu et al., I.Kashiwakura et al., D.Iizuka et al., S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., I.Kashiwakura et al., O.Inanami et al.]
通讯作者: O.Inanami et al.
Radioprotective synergistic action of cytokines on the clonalgrowth of x-irradiated human megakaryocytic progenitor cells
细胞因子对X射线照射的人巨核细胞祖细胞克隆生长的辐射防护协同作用
DOI: --
发表时间: 2003
期刊: 12^<th> International Congress of Radiation Research Final program & book of abstracts
影响因子: --
作者: [I.Kashiwakura et al., S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., T.Hamasu et al., I.Kashiwakura et al., D.Iizuka et al., 柏倉 幾郎, 柏倉 幾郎, S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., D.Iizuka et al., I.Kashiwakura et al., I.Kashiwakura et al., I.Kashiwakura et al., T.Hamasu et al., I.Kashiwakura et al., D.Iizuka et al., S.Monzen et al., I.Kashiwakura et al., I.Kashiwakura et al., I.Kashiwakura et al., O.Inanami et al., S.J.Hossinimehr et al., 柏倉 幾郎, 柏倉 幾郎, I.Kashiwakura et al., O.Inanami et al., I.Kashiwakura et al., I.Kashiwakura et al., 柏倉 幾郎, 柏倉 幾郎 他, I.Kashiwakura et al., I.Kashiwakura et al., 柏倉 幾郎, I.Kashiwakura et al., I.Kashiwakura et al.]
通讯作者: I.Kashiwakura et al.
DOI: 10.1007/s10495-005-1888-x
发表时间: 2005-05-01
期刊: APOPTOSIS
影响因子: 7.2
作者: [Hamasu, T, Inanami, O, Kuwabara, M]
通讯作者: Kuwabara, M
共 29 条
    Protective effects of a combination of multiple pharmaceutical drugs on the survival of mice exposed to lethal ionizing radiation
    • 批准号:
      24659553
    • 项目类别:
      Grant-in-Aid for Challenging Exploratory Research
    • 资助金额:
      $2.33万
    • 财政年份:
      2012
    • 负责人:
      KASHIWAKURA Ikuo
    • 依托单位:
    The development of multifunctional drug for magnetic resonance imaging diagnosis that uses metallic complex liquid crystal compound
    • 批准号:
      22659216
    • 项目类别:
      Grant-in-Aid for Challenging Exploratory Research
    • 资助金额:
      $2.08万
    • 财政年份:
      2010
    • 负责人:
      KASHIWAKURA Ikuo
    • 依托单位:
    The identification of factor (s) which regulate individual radiosensitivity of human hematopoietic stem/progenitor cells and its application
    • 批准号:
      21390336
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $6.99万
    • 财政年份:
      2009
    • 负责人:
      KASHIWAKURA Ikuo
    • 依托单位:
    Placental/Umbilical cord blood-derived mesenchymal stem cell-likestroma cells support the hematopoietic recovery of X-irradiated human CD34+ cells
    • 批准号:
      18390327
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $5.67万
    • 财政年份:
      2006
    • 负责人:
      KASHIWAKURA Ikuo
    • 依托单位:
    海外基金