Effects of Interleukins and Hemopoietic Growth Factors on Proliferation of Multipotent Stem Cell and Leukemic Cells.

白细胞介素和造血生长因子对多能干细胞和白血病细胞增殖的影响。

基本信息

批准号：
01480258
负责人：
NAKAHATA Tatsutoshi
金额：
$ 4.48万
依托单位：
Shinshu 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：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

Effects of interleukins (IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9) and various hemopoietic growth factors including granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulation factor (GM-CSF), macrophage colony stimulating factor (M-CSF), erythropoietin (Epo), leukemia inhibitory factor (LIF), stem cell factor (SCF), and interferon- (IFN-) on proliferation of multipotential hemopoietic stem cells and leukemic cells were examined using vitro methylcellulose cultures.In murine, our extensive serum-free culture suggests that the existence of primitive hemopoietic progenitors which require both IL-3 and IL-6 for development, and that some primitive hemopoietic progenitors requiring both IL-3 and IL-6 for the substntaial growth may be unable to survive under the condition of IL-3 alone.Murine bone marrow cells cultured with both IL-3 and IL-6 for 6 days in suspension culture were found to exhibit a highly capacity to reconstitute the hemopoietic system of sublethally-irradiated mice than untreated bone marrow cells. The number of colony-forming units in the spleen (CFU-S) increaseased up to 400 times after 5 weeks of culture in the presence of both IL-3 and IL-6. In experiments using human cord blood or bone marrow cells, a synergistic effect of IL-3 and IL-6 on proliferation of hemopoietic progenitors in short-term cultures was observed in some samples. These results the possible clinical application of in vitro stem cell expansion to bone marrow transplantion.We also found that recombinant human IL-6 stimulates murine and human megakaryocyte colonies dose-dependently synergistically with IL-3. IL-6 alone stimulated no only in vivo maturation of megakaryocytes and platelets production in primates treated with IL-6 but also in vitro maturation of human megakaryocytes.

白细胞介素（IL-1、IL-2、IL-4、IL-5、IL-6、IL-7、IL-9）和各种造血生长因子（包括粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、巨噬细胞集落刺激因子（M-CSF）、促红细胞生成素（Epo）、白血病抑制因子（LIF）、干细胞使用体外甲基纤维素培养物检查了因子（SCF）和干扰素（IFN-）对多能造血干细胞和白血病细胞增殖的影响。在小鼠中，我们广泛的无血清培养表明存在需要IL和IL的原始造血祖细胞-3和IL-6进行发育，并且一些需要IL-3和IL-6进行实质生长的原始造血祖细胞可能无法在这种条件下存活单独的IL-3。与未处理的骨髓细胞相比，在悬浮培养物中与IL-3和IL-6一起培养6天的小鼠骨髓细胞被发现表现出重建亚致死照射小鼠造血系统的高能力。在 IL-3 和 IL-6 存在的情况下培养 5 周后，脾脏中集落形成单位的数量 (CFU-S) 增加了 400 倍。在使用人脐带血或骨髓细胞的实验中，在一些样品中观察到IL-3和IL-6对短期培养物中造血祖细胞增殖的协同作用。这些结果为体外干细胞扩增在骨髓移植中的临床应用提供了可能。我们还发现重组人IL-6与IL-3以剂量依赖性协同方式刺激小鼠和人巨核细胞集落。单独的IL-6不仅刺激用IL-6处理的灵长类动物中巨核细胞的体内成熟和血小板产生，而且还刺激人巨核细胞的体外成熟。