Schwartz G N, Warren M K, Sakano K, Szabo J M, Kessler S W, Pashapour A, Gress R E, Perdue J F
Transplantation Therapy Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Stem Cells. 1996 May;14(3):337-50. doi: 10.1002/stem.140337.
This report presents the results of studies investigating the effect of insulin-like growth factor II (IGF-II) on the proliferation and differentiation of CD34+ bone marrow cells in serum-substituted liquid cultures. Bone marrow cells were enriched for CD34+ cells and then placed in liquid cultures supplemented with either interleukin 3 (IL-3) or IL-3 and c-kit ligand with and without the addition of IGF-II. When CD34+ cells were incubated with IL-3, cellularity increased throughout four weeks of culture. Cellularity was twofold greater when cultures also contained IGF-II. IGF-II also promoted an increase in cellularity in cultures with IL-3 and c-kit ligand. In combination with IL-3 or IL-3 and c-kit ligand, IGF-II promoted an earlier differentiation of granulocytes, as well as an increase in the number of megakaryocyte lineage cells. There were approximately two-fold more colony-forming units for granulocytes and macrophages (CFU-GM) and burst-forming units for erythroid cells (BFU-E) in cultures containing both IL-3 and IGF-II than in cultures with IL-3 alone. These results demonstrate that in cytokine-supplemented media, physiological concentrations of IGF-II augmented both the proliferation and differentiation of CD34+ bone marrow cells while maintaining a greater number of progenitor cells. To identify the receptors through which IGF-II enhances in vitro hematopoiesis, IGF-II was substituted with one of the mutant forms of IGF-II that selectively interacts with either IGF-II/CIM6-P receptors or with IGF-I and insulin receptors. The results with the mutant forms of IGF-II demonstrate that IGF-II augments in vitro hematopoiesis primarily through its interaction with IGF-I and possibly insulin receptors, rather than IGF-II/CIM6-P receptors.
本报告展示了关于胰岛素样生长因子II（IGF-II）对血清替代液体培养中CD34+骨髓细胞增殖和分化影响的研究结果。骨髓细胞经富集获得CD34+细胞，然后置于添加白细胞介素3（IL-3）或IL-3与c-kit配体的液体培养中，同时添加或不添加IGF-II。当CD34+细胞与IL-3一起培养时，在整个四周的培养过程中细胞数量增加。当培养物中也含有IGF-II时，细胞数量增加了两倍。IGF-II还促进了含有IL-3和c-kit配体的培养物中细胞数量的增加。与IL-3或IL-3和c-kit配体联合使用时，IGF-II促进了粒细胞的早期分化以及巨核细胞系细胞数量的增加。同时含有IL-3和IGF-II的培养物中粒细胞和巨噬细胞集落形成单位（CFU-GM）以及红系爆式集落形成单位（BFU-E）的数量比仅含有IL-3的培养物中大约多两倍。这些结果表明，在补充了细胞因子的培养基中，生理浓度的IGF-II增强了CD34+骨髓细胞的增殖和分化，同时维持了更多的祖细胞数量。为了确定IGF-II增强体外造血作用所通过的受体，将IGF-II替换为选择性地与IGF-II/CIM6-P受体或与IGF-I和胰岛素受体相互作用的IGF-II突变形式之一。IGF-II突变形式的结果表明，IGF-II主要通过与IGF-I以及可能的胰岛素受体相互作用来增强体外造血作用，而不是通过与IGF-II/CIM6-P受体相互作用。
