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The effect of oxygen concentrations on the differentiation and proliferation of hematopoietic stem cells

氧浓度对造血干细胞分化增殖的影响

基本信息

批准号：
59480261
负责人：
YAMADA Hideo
金额：
$ 3.9万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1984
资助国家：
日本
起止时间：
1984 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-59480261/
关键词：
oxygen tension hematopoietic stem cells oxygen toxicity CFU-mix BFU-E CFU-E CFU-GM CFU-F

项目摘要

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.

从健康和疾病两个方面系统地研究了氧分压对人造血干细胞增殖的影响。所有正常造血祖细胞(CFU-Mix、BFU-E、CFU-E和CFU-GM)在低氧分压(5%和10%)下的集落生长均比在空气中培养的促进。CFU-E的增强作用最强，其次是CFU-GM、BFU-E和CFU-Mix。除造血干细胞外，CFU-F(成纤维细胞)作为骨髓基质细胞的一种成分，在低氧压条件下也表现出促进集落生长的作用。在氧分压降低时，BFU-E和CFU-E对促红细胞生成素(EPO)的敏感性以及CFU-GM对CSF的敏感性显著增加，这可能是促进其祖细胞集落生长的机制之一。另一方面，在空气中加入超氧化物歧化酶(SOD)后，CFU-E的菌落数量可能通过减少对CFU-E的氧毒性而呈剂量依赖性增加。在针对血液病的研究中，在真性红细胞增多症、骨髓增生异常综合征(MDS)和白血病方面取得了有趣的结果。未加EPO的真性红细胞增多症、阵发性睡眠性血红蛋白尿、慢性粒细胞白血病、MDS和缺铁性贫血的“内源性”CFU-E集落降低氧分压的发生率较高，且显著增加。在真性红细胞增多症中，CFU-E和BFU-E的EPO量效曲线在低氧压培养中进一步左移。在大多数MDS病例中，降低氧分压可显著促进CFU-E集落生长，在某些病例中CFU-E对EPO的敏感性增加。