Protective Effect of the c-mpl Agonist Romiplostim on Megakaryocytopoiesis of Human CD34+ Hematopoietic Progenitor Cells Exposed to Ionizing Radiation.
Protective Effect of the c-mpl Agonist Romiplostim on Megakaryocytopoiesis of Human CD34+ Hematopoietic Progenitor Cells Exposed to Ionizing Radiation.
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c-mpl 激动剂 Romiplostim 对暴露于电离辐射的人 CD34 造血祖细胞巨核细胞生成的保护作用。
DOI：
10.1089/jir.2017.0104
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Kashiwakura I
中科院分区：
文献类型：
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作者：
Monzen S;Kimura S;Yamaguchi M;Kashiwakura I
血小板生成刺激蛋白，骨髓增殖性白血病病毒原癌基因（Mpl）配体romiplostim（RP），目前在许多国家被批准作为特发性血小板减少性紫癜的治疗药物。尽管已经研究了初始MPL配体血小板生成素(TPO)对受辐射的人类造血干细胞的巨核细胞再生的作用，但关于RP作用的报道很少。在本研究中，将胎盘脐带血中新鲜制备的未照射和 2 Gy X 照射的人 CD34 阳性 (CD34+) 细胞与 RP 和各种细胞因子结合培养。结果发现，RP 对未照射 CD34+ 细胞增殖的影响与 TPO 相当。然而，与TPO相比，RP对巨核细胞祖细胞集落形成的刺激活性明显较低。关于RP与各种细胞因子的作用，目前的结果表明，RP与白细胞介素3（IL-3）或IL-3加干细胞因子（SCF）的组合对X射线照射的CD34 + 细胞的细胞增殖、巨核细胞生成、血小板生成和巨核细胞集落形成具有高度再生作用。本研究表明，人重组 RP 对 X 射线照射的人 CD34+ 细胞的人巨核细胞再生具有潜在影响，并与 IL-3 和 IL-3 加 SCF 协同作用，正如在 TPO 中观察到的那样。
A thrombopoiesis-stimulating protein, the myeloproliferative leukemia virus protooncogene (Mpl) ligand romiplostim (RP), is currently approved as a therapeutic agent for idiopathic thrombocytopenic purpura in many countries. Although the action of the initial MPL ligand thrombopoietin (TPO) on human megakaryocytic regeneration from irradiated human hematopoietic stem cells has been examined, there are few reports on the action of RP. In the present study, freshly prepared nonirradiated and 2-Gy X-irradiated human CD34 positive (CD34+) cells from placental umbilical cord blood were cultured with a combination of RP and various cytokines. As a result, the effect of RP on cell proliferation of nonirradiated CD34+cells was found to be comparable to that of TPO. However, the stimulating activity of RP on megakaryocytic progenitor-derived colony formation was markedly lower compared with TPO. Regarding the action of RP with various cytokines, the present results showed that a combination of RP with interleukin-3 (IL-3) or IL-3 plus stem cell factor (SCF) showed a high regenerative effect on cell proliferation, megakaryopoiesis, thrombopoiesis, and megakaryocyte colony formation from X-irradiated CD34+cells. The present study showed that human recombinant RP has potential effects on human megakaryocytic regeneration from X-irradiated human CD34+cells and synergistically acts with IL-3 and IL-3 plus SCF, just as observed with TPO.