Hénon P R, Becker M
Institut de Recherche en Hématologie et Transfusion, Hôpital du Hasenrain, Mulhouse, France.
Stem Cells. 1993 Jul;11 Suppl 2:65-71. doi: 10.1002/stem.5530110811.
The use of cytokines to improve peripheral blood stem cell enhancement and recruitment has recently received close attention. Three main cytokines have been, or are still being, investigated in this way in human clinical trials so far: recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), granulocyte CSF (rhG-CSF) and interleukin 3 (IL-3). While cytokines used alone appear undoubtedly capable of a marked peripheral blood stem cell (PBSC) enhancement, their combination with a chemotherapy priming often increases this phenomenon. This is particularly evident with rhIL-3, which is an earlier acting cytokine than rhGM-CSF and rhG-CSF. rhIL-3 priming alone leads to only a minor elevation of circulating progenitor cells, while its combination with chemotherapy and/or a late acting cytokine may allow enhancement and recruitment of large amounts of PBSC. The effect of cytokines on PBSC enhancement may also be at least partially thwarted by various factors. Additionally, their adequate dosage often remains uncertain. So it is presently too early to determine what is actually the most appropriate cytokine or cytokine combination to improve PBSC enhancement. Also the risk of stimulation of tumor clonogenic cells in some malignant diseases remains, and the experimenters should be as cautious as possible to not jeopardize the patients' safety.
近年来,使用细胞因子来提高外周血干细胞的扩增和募集受到了密切关注。迄今为止,在人类临床试验中,已有三种主要的细胞因子正在或仍在以这种方式进行研究:重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)、粒细胞集落刺激因子(rhG-CSF)和白细胞介素3(IL-3)。虽然单独使用细胞因子无疑能够显著提高外周血干细胞(PBSC)数量,但它们与化疗预处理联合使用时,这种现象往往会加剧。这在rhIL-3中尤为明显,它是一种比rhGM-CSF和rhG-CSF作用更早的细胞因子。单独使用rhIL-3预处理只会使循环祖细胞略有升高,而将其与化疗和/或一种作用较晚的细胞因子联合使用,可能会促使大量外周血干细胞的扩增和募集。细胞因子对外周血干细胞扩增的作用也可能至少部分地受到各种因素的阻碍。此外,它们的适当剂量往往仍不确定。因此,目前确定哪种细胞因子或细胞因子组合实际上最适合提高外周血干细胞扩增还为时过早。而且在某些恶性疾病中,刺激肿瘤克隆形成细胞的风险依然存在,实验人员应尽可能谨慎,以免危及患者安全。