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

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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.