| Project/Area Number |
12672115
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Hokkaido College of Pharmacy |
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Principal Investigator |
KASHIWAKURA Ikuo Hokkaido College of Pharmacy, Department of Pharmacy, Associate Professor, 薬学部, 助教授 (00177370)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Miho Hokkaido College of Pharmacy, Department of Pharmacy, Assistant, 薬学部, 助手 (00182105)
INANAMI Osamu Hokkaido University, Graduate School of Veterinary Medicine, Associate Professor, 大学院・獣医学研究科, 助教授 (10193559)
KUWABARA Mikinori Hokkaido University, Graduate School of Veterinary Medicine, Professor, 大学院・獣医学研究科, 教授 (10002081)
TAKAHASHI Tsuneo The Institute of Medical Science, The University of Tokyo, Cell Processing, Professor, 医科学研究所・細胞プロセッシング研究部門, 教授 (50291307)
TAKAGI Yoshinari Hokkaido College of Pharmacy, Department of Pharmacy, Professor, 薬学部, 教授 (70094852)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | X-iradiation / Hematopoietic stem cell / CD34^+ cell / Megakaryocytic progenitor cell / Placental / umbilical cord blood / Peripherral blood / Cytokine / Thrombopoietin / thrombopoietin / Amifostine |
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| Research Abstract |
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.
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