Dexter T M, Heyworth C M
Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital, Withington, Manchester, UK.
Eur J Clin Microbiol Infect Dis. 1994;13 Suppl 2:S3-8. doi: 10.1007/BF01973595.
In the absence of appropriate growth factors, for example interleukin-3 or GM-CSF, cultured bone marrow stem cells die by a process known as apoptosis or programmed cell death. Apoptosis may occur in vivo when concentrations of specific growth factors are limiting and may be a means of regulating cell numbers. Growth factors are also essential for proliferation of bone marrow stem cells but differentiation can occur, provided there is a survival stimulus in the absence of growth factors. Combinations of growth factors may be synergistic in stimulating the survival and proliferation of multipotent stem cells. Although neither stem cell factor, nor GM-CSF alone can significantly induce the proliferation of stem cells, the combination induces the proliferation of these cells. Committed progenitor cells such as granulocyte-macrophage colony-forming cells, however, are stimulated to proliferate by GM-CSF alone, while stem cell factor in combination with GM-CSF results in only a slight additive effect. To date, most research has concentrated on the growth stimulatory factors. GM-CSF has an important role in the reversal of chemotherapy-induced myelosuppression in cancer patients and in other bone marrow disorders. A number of growth inhibitory molecules have now been identified, such as macrophage inhibitory protein-1 alpha. In the future, it is possible that improvements in cure rates may be achieved in cancer patients by combining the growth inhibitory factors with the stimulatory factors. Inhibitory factors may be given before chemotherapy to prevent toxicity and stimulatory factors may be given afterwards to treat neutropenic patients.
在缺乏合适的生长因子（例如白细胞介素 -3 或粒细胞 - 巨噬细胞集落刺激因子）的情况下，培养的骨髓干细胞会通过一种称为凋亡或程序性细胞死亡的过程死亡。当特定生长因子的浓度受到限制时，凋亡可能在体内发生，并且可能是调节细胞数量的一种方式。生长因子对于骨髓干细胞的增殖也是必不可少的，但只要在缺乏生长因子时有存活刺激，分化就可能发生。生长因子的组合在刺激多能干细胞的存活和增殖方面可能具有协同作用。虽然单独的干细胞因子或粒细胞 - 巨噬细胞集落刺激因子都不能显著诱导干细胞增殖，但两者的组合可诱导这些细胞增殖。然而，定向祖细胞，如粒细胞 - 巨噬细胞集落形成细胞，仅被粒细胞 - 巨噬细胞集落刺激因子刺激增殖，而干细胞因子与粒细胞 - 巨噬细胞集落刺激因子联合使用仅产生轻微的相加效应。迄今为止，大多数研究都集中在生长刺激因子上。粒细胞 - 巨噬细胞集落刺激因子在癌症患者化疗诱导的骨髓抑制逆转以及其他骨髓疾病中具有重要作用。现在已经鉴定出一些生长抑制分子，如巨噬细胞抑制蛋白 -1α。未来，通过将生长抑制因子与刺激因子联合使用，癌症患者的治愈率有可能提高。抑制因子可在化疗前给予以预防毒性，刺激因子可在化疗后给予以治疗中性粒细胞减少的患者。
