| Project/Area Number |
59480261
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Nagoya University |
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Principal Investigator |
YAMADA Hideo Nagoya University School of Medicine, 医学部, 講師 (40022876)
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| Co-Investigator(Kenkyū-buntansha) |
山雄 久美 名古屋大学, 医学部, 医員
MURATE Takeshi Nagoya University School of Medcine, 医学部, 医員 (30239537)
KATO Taiji Nagoya University School of Medicine, 医学部, 医員 (60094364)
前田 秀明 名古屋大学, 医学部, 医員
UTSUMI Makoto Nagoya University School of Medicine, 医学部, 助手 (20176712)
MAEDA Hideaki Nagoya University School of Medicine
YAMAO Hisami Nagoya University School of Medicine
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1986: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1985: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1984: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | oxygen tension / hematopoietic stem cells / oxygen toxicity / CFU-mix / BFU-E / CFU-E / CFU-GM / CFU-F |
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| Research Abstract |
The effect of oxygen tensions on the proliferation of human haematopoietic stem cells were systematically studied in health and diseases. All normal hematopoietic progenitor cells ( CFU-mix,BFU-E,CFU-E and CFU-GM) investigated showed the enhanced colony growth at low oxygen tensions ( 5% and 10% ) in comparison to the cultures in air gas. CFU-E showed the highest enhancement,followed in order by CFU-GM,BFU-E and CFU-mix. Besides haematopoietic stem cells,CFU-F (fibroblast) as a component of marrow stromal cells also showed the enhanced colony growth at reduced oxygen tension cultures. In reduced oxygen tension,the sensitivity of BFU-E and CFU-E to erythropoietin (EPO) as well as that of CFU-GM to CSF were significantly increased and they can be one of the mechanisms for the enhanced colony growth of their progenitors. On the other hand,the addition of superoxide dismutase (SOD) to the CFU-E colony growth in air gave rise to the dose-dependent increment of colony numbers possibly through reduced oxygen toxicity to CFU-E.
Among the studies performed on hematological disorders,interesting results in polycythemia vera, myelodysplastic syndrome (MDS) and leukemias were obtained. "Endogenous" CFU-E colonies without addition of EPO in polycythemia vera,paroxysmal nocturnal hemoglobinuria,chronic myegenous leukemia ,MDS and iron deficiency anemia showed higher incidence and remarkable increase of the colonies in reduced oxygen tension. In polycythemia vera,EPO dose-response curves of CFU-E and BFU-E were further shifted to the left in reduced oxygen tension cultures. In most cases of MDS,remarkable enhancement of CFU-E colony growth was observed in reduced oxygen tension and in some cases the increased EPO sensitivity of CFU-E was demonstrated.
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