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Action of optimum cytokine for the recovery of X-irradiated human hematopoietic stem and progenitor cells

最佳细胞因子对 X 射线照射的人类造血干细胞和祖细胞恢复的作用

基本信息

批准号：
12672115
负责人：
KASHIWAKURA Ikuo
金额：
$ 1.98万
依托单位：
Hokkaido College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672115/
关键词：
X-iradiation Hematopoietic stem cell CD34^+ cell Megakaryocytic progenitor cell Placental umbilical cord blood Peripherral blood Cytokine Thrombopoietin thrombopoietin Amifostine

项目摘要

We obtained the results from the project titled "Action of optimum cytokine for the recovery of X-irradiated human hematopoietic stem and progenitor cells" for the period from 2000 to 2001. The following points were clarified.(1) Human placental/umbilical cord blood (CB) CD34^+ CFU-Meg (megakaryocyte colony-forming units) is more radiosensitive than the other myeloid hematopoietic progenitor cells, including erythroid burst-forming units, granulocyte-macrophage colony-forming units and granulocyte-erythroid-macrophage-megakaryocyte colony-forming units.(2) The proportion of large megakaryocyte colonies, immature CFU-Meg, was 60 - 78% of the total number of colonies in all combinations we tested. The immature CFU-Meg is more radiosensitive than the mature CFU-Meg. In contrast, the total CFU-Meg from normal human peripheral blood (PB) is more radiosensitive than those in CB, despite the predominance of mature CFU-Meg in PB.(3) The combination of cytokines, including thrombopoietin (TPO), interleukin-3 (IL-3) and stem cell factor (SCF), is effective for the radiation survival of CB CD34^+ CFU-Meg in all cytokine combinations we tested. In the case of PB CD34^+ CFU-Meg, the combination of TPO plus IL-3 is most effective for the radiation survival of CFU-Meg than the others.(4) The result indicated that part of the synergistic effect of TPO plus SCF can be explained by the activation of mitogen-activated protein kinase and extracellular-signal-regulated protein kinase and the suppression of caspase cascade.(5) The synergistic effect of TPO and IL-3 for the radiation survival of PB CD34^+ CFU-Meg is involved the JAK/STAT (janus kinase/signal transducer and activator of transcription), however, no involvement of phosphatidylinositol-3-kinase-related signals transduction is shown.

我们从2000年至2001年期间获得了题为“最佳细胞因子对X射线照射的人造血干细胞和祖细胞恢复的作用”的项目的结果。澄清了以下几点。(1)人胎盘/脐带血（CB）CD 34 ^+ CFU-Meg（巨核细胞集落形成单位）比其他骨髓造血祖细胞（包括红系爆发集落形成单位、粒细胞-巨噬细胞集落形成单位和粒细胞-红系-巨噬细胞-巨核细胞集落形成单位）更敏感。(2)在我们测试的所有组合中，大巨核细胞集落（未成熟CFU-Meg）的比例为集落总数的60 - 78%。未成熟的CFU-Meg比成熟的CFU-Meg更敏感。相反，尽管正常人外周血（PB）中成熟CFU-Meg占优势，但其总CFU-Meg比CB中的CFU-Meg更放射敏感。(3)在我们测试的所有细胞因子组合中，包括血小板生成素（TPO）、白细胞介素-3（IL-3）和干细胞因子（SCF）的细胞因子组合对CB CD 34 ^+ CFU-Meg的辐射存活有效。在PB CD 34 ^+ CFU-Meg的情况下，TPO + IL-3的组合对CFU-Meg的辐射存活最有效。(4)结果表明，TPO与SCF协同作用的部分机制可能是通过激活丝裂原活化蛋白激酶（MAPK）和细胞外信号调节蛋白激酶（ERK），抑制caspase级联反应而实现的。(5)TPO和IL-3对PB CD 34 ^+ CFU-Meg辐射存活的协同作用涉及JAK/STAT（janus kinase/signal transducer and activator of transcription），而没有显示出涉及磷脂酰肌醇-3-激酶相关的信号转导。