2005 Fiscal Year Final Research Report Summary
The study of therapy for radiation-induced thrombocytopenia by using ex vivo expanded-megakaryocyte prepared from auto hematopoietic stem cell.
| Project/Area Number |
15591253
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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 |
Radiation science
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| Research Institution | Hirosaki University |
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Principal Investigator |
KASHIWAKURA Ikuo Hirosaki University School of Medicine, Department of Radiological Technology, Professor, 医学部, 教授 (00177370)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Kei Hirosaki University School of Medicine, Department of Vascular Biology, Institute of Brain Science, Professor, 医学部, 教授 (20125438)
TAKAHASHI Tsuneo The University of Tokyo, Cell Processing Department, Institute of Medical Science, Professor, 医科学研究所, 教授 (50291307)
ABE Yoshinao Hirosaki University School of Medicine, Laboratory of Radiology, Professor, 医学部, 教授 (10167950)
KUWABARA Mikinori Hokkaido University, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Professor, 大学院・獣医学研究科, 教授 (10002081)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Irradiation / Hematopoietic stem cell / Cytokie / Megakaryocytic progenitor cell / Regeneration / Platelet |
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| Research Abstract |
1.CD34 antigen is a novel marker for human hematopoietic stem/progenitor cells. Two cell fractions, CD34^<low> and CD34^<high>, were prepared from steady-state human peripheral blood (PB) on the basis of CD34 antigen expression. The content of CD34^+CD45^+ cells in the CD34^<low> and CD34^<high> cell fractions was 74.8% and 88.8%, respectively, and the frequency of thrombopoietin (TPO)-supported colony-forming unit megakaryocytes (CFU-Meg) in the CD34^<low> cell fraction was 1.9 times higher than that in CD34^<high>. The CFU-Meg in CD34^<high> were more radiosensitive than those in CD34^<low>, indicating that steady-state human PB contains different types of CFU-Meg. TPO plus interleukin-3 was the optimal combination for survival of both types of CFU-Meg after X irradiation. These results suggest that multiple combinations with TPO will be helpful in cytokine therapy for post-irradiation thrombocytopenia.
2.Mature megakaryocytes induced from the culture of PB CD34^+ cells with TPO are s
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hown high radio sensitivity, however, normal pro-platelet formation occurred after X irradiation. These results suggest that the influence of X irradiation to the end of thrombopoiesis is small.
3.Low concentration of Epigallocatechin-3-gallate (EGCg,100 nM), a major green tea polyphenol, reduce the risk factor from radiation damage in megakaryocytopoiesis, suggesting the medical application of EGCg for the treatment of thrombocytopenia.
4.CFU-Meg are more radiosensitive progenitors to cabon ion beam than X-ray. The induction of γ-H2AX, a marker of DNA double strand break (DSB), by carbon ion beam in CD34^+ cells was not enhanced by cytokine treatment such as that of X-ray. These results showed that the DSB repair of CFU-Meg by cytokine was lesser in progenitors to carbon ion beam than X-ray.
5.A combination of IL-3 plus TPO would be an optimal choice for the regeneration of megakaryocytopoiesis and thrombopoiesis from X-irradiated stem cells. Our results suggest that nearly normal megakaryocytopoiesis and thrombopoiesis can be induced from X-irradiated stem cells by stimulation with appropriate cytokine combinations. Less
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Research Products
(40 results)
