Takahashi Kenji, Monzen Satoru, Yoshino Hironori, Abe Yoshinao, Eguchi-Kasai Kiyomi, Kashiwakura Ikuo
Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori, Japan.
J Radiat Res. 2008 Jul;49(4):417-24. doi: 10.1269/jrr.07132. Epub 2008 May 27.
To evaluate whether the continuous treatment of two cytokine combinations is effective in megakaryocytopoiesis and thrombopoiesis in hematopoietic stem/progenitor cells exposed to heavy ion beams, the effects of a 2-step culture by a combination of recombinant human interleukin-3 (IL-3) + stem cell factor (SCF) + thrombopoietin (TPO), which just slightly protected against carbon-ion beam-induced damages, and a combination of IL-3 + TPO, which selectively stimulated the differentiation of the hematopoietic stem/progenitor cells to megakaryocytes and platelets, were examined. CD34(+)-hematopoietic stem/progenitor cells isolated from the human placental and umbilical cord blood were exposed to carbon-ion beams (LET = 50 keV/microm) at 2 Gy. These cells were cultured under three cytokine conditions. The number of megakaryocytes, platelets and hematopoietic progenitors were assessed using a flow cytometer and a clonogenic assay at 14 and 21 days after irradiation, respectively. However, the efficacy of each 2-step culture was equal or lower than that of using the IL-3 + SCF + TPO combination alone and the 2-step culture could not induce megakaryocytes and platelets from hematopoietic stem/progenitor cells exposed to high LET-radiation such as carbon-ion beams. Therefore, additional cytokines and/or hematopoietic promoting compounds might be required to overcome damage to hematopoietic cells by high LET radiation.
为了评估两种细胞因子组合的持续处理对暴露于重离子束的造血干细胞/祖细胞的巨核细胞生成和血小板生成是否有效，研究了重组人白细胞介素-3（IL-3）+干细胞因子（SCF）+血小板生成素（TPO）组合（仅能轻微保护免受碳离子束诱导的损伤）以及IL-3 + TPO组合（选择性刺激造血干细胞/祖细胞向巨核细胞和血小板分化）进行两步培养的效果。从人胎盘和脐带血中分离出的CD34(+)造血干细胞/祖细胞接受2 Gy的碳离子束（传能线密度= 50 keV/μm）照射。这些细胞在三种细胞因子条件下培养。分别在照射后14天和21天使用流式细胞仪和集落形成试验评估巨核细胞、血小板和造血祖细胞的数量。然而，每种两步培养的效果与单独使用IL-3 + SCF + TPO组合的效果相当或更低，并且两步培养不能从暴露于高传能线密度辐射（如碳离子束）的造血干细胞/祖细胞诱导产生巨核细胞和血小板。因此，可能需要额外的细胞因子和/或造血促进化合物来克服高传能线密度辐射对造血细胞的损伤。
