de Revel T, Appelbaum F R, Storb R, Schuening F, Nash R, Deeg J, McNiece I, Andrews R, Graham T
Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092.
Blood. 1994 Jun 15;83(12):3795-9.
The effects of recombinant canine granulocyte colony-stimulating factor (rcG-CSF) and recombinant canine stem cell factor (rcSCF), a c-kit ligand, on the circulation of hematopoietic progenitor and stem cells were studied in a canine model. Administration of rcG-CSF (10 micrograms/kg) for 7 days led to a 5.4-fold increase in CFU-GM/mL of blood, while 7 days of rcSCF (200 micrograms/kg) led to an 8.2-fold increase. Although treatment with low-dose rcSCF (25 micrograms/kg) had no effect on the level of peripheral blood progenitors, 7-day exposure to a combination of G-CSF plus low dose SCF led to a 21.6-fold increase (P = .03). To assess the ability of these factors to increase the circulation of cells capable of rescuing animals after lethal total body irradiation (TBI), 1 x 10(8) peripheral blood mononuclear cells (PBMC)/kg were collected and cryopreserved from animals after 7 days of treatment with G-CSF, SCF or a combination of the two. One month later, animals were exposed to 9.2 Gy TBI and transplanted with the previously collected cells. Control animals transplanted with 1 x 10(8) PBMC/kg collected without pretreatment died with marrow aplasia 11 to 29 days after TBI as did animals treated with only low-dose SCF before cell collection. In contrast, all animals given PBMC collected after G-CSF, high-dose SCF, or a combination of G-CSF plus low-dose SCF recovered granulocyte function. Recovery to 500 granulocytes/microL after transplant took 17, 18.8, and 13.6 days, respectively, (P = .056 for the difference between the combination G-CSF-SCF group and the other two groups). In both the G-CSF and SCF groups, 4 of 5 animals completely recovered while 1 of 5 in each group died with prolonged thrombocytopenia. In the combination group, all 5 animals became long-term survivors. These studies demonstrate that both G-CSF and SCF dramatically increase the level of peripheral blood hematopoietic progenitor and stem cells and support the view that these factors can act synergistically.
在犬类模型中研究了重组犬粒细胞集落刺激因子（rcG-CSF）和重组犬干细胞因子（rcSCF，一种c-kit配体）对造血祖细胞和干细胞循环的影响。给予rcG-CSF（10微克/千克）7天导致血液中CFU-GM/毫升增加5.4倍，而给予rcSCF（200微克/千克）7天导致增加8.2倍。虽然低剂量rcSCF（25微克/千克）治疗对外周血祖细胞水平没有影响，但7天暴露于G-CSF加低剂量SCF的组合导致增加21.6倍（P = 0.03）。为了评估这些因子增加能够在致死性全身照射（TBI）后拯救动物的细胞循环的能力，在给予G-CSF、SCF或两者组合治疗7天后，从动物中收集1×10⁸外周血单个核细胞（PBMC）/千克并冷冻保存。1个月后，动物接受9.2 Gy的TBI并移植先前收集的细胞。移植1×10⁸ PBMC/千克且未进行预处理的对照动物在TBI后11至29天死于骨髓再生障碍，细胞收集前仅用低剂量SCF治疗的动物也是如此。相比之下，所有接受G-CSF、高剂量SCF或G-CSF加低剂量SCF组合后收集的PBMC的动物恢复了粒细胞功能。移植后恢复到500个粒细胞/微升分别需要17、18.8和13.6天，（G-CSF-SCF组合组与其他两组之间的差异P = 0.056）。在G-CSF组和SCF组中，5只动物中有4只完全恢复，而每组中有1只死于血小板减少症延长。在组合组中，所有5只动物都成为长期存活者。这些研究表明，G-CSF和SCF都能显著增加外周血造血祖细胞和干细胞的水平，并支持这些因子可协同作用的观点。
