Sawada K, Sato N, Notoya A, Tarumi T, Yasukouchi T, Yamaguchi M, Kohno M, Mikuni C, Koike T
Department of Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
Eur J Haematol. 1995 Feb;54(2):85-94. doi: 10.1111/j.1600-0609.1995.tb01773.x.
To investigate the role of colony stimulating factors (CSFs) in the proliferation and differentiation of progenitor cells from myelodysplastic syndromes (MDS), marrow progenitor cells from 18 MDS patients were highly purified using CD34 monoclonal antibody and immunomagnetic microspheres (MDS CD34+ cells). These cells were cultured in serum-free medium with various combinations of five colony stimulating factors (CSFs): recombinant human interleukin-3 (rIL-3), granulocyte/macrophage-CSF (rGM-CSF), granulocyte-CSF (rG-CSF), macrophage-CSF (rM-CSF), and erythropoietin (rEP). Among the tested CSFs, such as rM-CSF, rG-CSF, rGM-CSF and rIL-3, a combination of the first three CSFs was the most effective stimulus for the proliferation of non-erythroid MDS progenitor cells. An increase of undifferentiated "blast" cell colonies in 5/18 MDS patients occurred and these 5 patients belonged to the high-risk group. In the presence of these three CSFs, rIL-3 had no effect on the proliferation and differentiation of MDS CD34+ cells; however, IL-3 was efficient for the proliferation of MDS CD34+ cells to the erythroid lineage. rGM-CSF or rIL-3 alone did not efficiently support proliferation and differentiation of CD34+ cells. M-CSF is present in normal human serum at a concentration of 550 +/- 110 U/ml, a concentration exceeding that used in this study (100 U/ml). Therefore, in vivo administration of G-CSF combined with GM-CSF to MDS patients may be one of the most effective CSF combinations for proliferation of MDS progenitor cells to the non-erythroid lineage. However, the effect on the capacity for differentiation was minimal, especially in patients belonging to the high-risk group.
为研究集落刺激因子（CSF）在骨髓增生异常综合征（MDS）祖细胞增殖和分化中的作用，采用CD34单克隆抗体和免疫磁珠对18例MDS患者的骨髓祖细胞进行高度纯化（MDS CD34+细胞）。将这些细胞在无血清培养基中与五种集落刺激因子（CSF）的不同组合进行培养：重组人白细胞介素-3（rIL-3）、粒细胞/巨噬细胞集落刺激因子（rGM-CSF）、粒细胞集落刺激因子（rG-CSF）、巨噬细胞集落刺激因子（rM-CSF）和促红细胞生成素（rEP）。在测试的CSF中，如rM-CSF、rG-CSF、rGM-CSF和rIL-3，前三种CSF的组合是对非红系MDS祖细胞增殖最有效的刺激。18例MDS患者中有5例未分化的“原始”细胞集落增加，这5例患者属于高危组。在这三种CSF存在的情况下，rIL-3对MDS CD34+细胞的增殖和分化没有影响；然而，IL-3对MDS CD34+细胞向红系的增殖有效。单独的rGM-CSF或rIL-3不能有效地支持CD34+细胞的增殖和分化。M-CSF在正常人血清中的浓度为550±110 U/ml，该浓度超过了本研究中使用的浓度（100 U/ml）。因此，对MDS患者体内给予G-CSF联合GM-CSF可能是使MDS祖细胞向非红系增殖的最有效的CSF组合之一。然而，对分化能力的影响最小，尤其是在高危组患者中。
