title: Effects of a 2-step culture with cytokine combinations on megakaryocytopoiesis and thrombopoiesis from carbon-ion beam-irradiated human hematopoietic stem/progenitor cells.
abstract: 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.
authors.affiliation: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Monzen
authors.forename: Hironori
authors.initials: H
authors.lastname: Yoshino
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Abe
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Eguchi-Kasai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
mesh_terms: D002250:Carbon Radioisotopes; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D016207:Cytokines / Q000008:administration & dosage*; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D020450:Heavy Ions; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology; D011829:Radiation Dosage; D034061:Thrombopoiesis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
chemical_list: D002250:Carbon Radioisotopes; D016207:Cytokines; D004338:Drug Combinations