Andrews R G, Briddell R A, Knitter G H, Rowley S D, Appelbaum F R, McNiece I K
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Blood. 1995 Jan 1;85(1):15-20.
We have previously shown that administration of low-dose recombinant human stem cell factor (rhSCF) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood than does administration of rhG-CSF alone. The purpose of the present study was to determine whether marrow repopulating cells are present in the blood of nonhuman primates administered low-dose rhSCF plus rhG-CSF, and if present, whether these cells engraft lethally irradiated recipients as rapidly as blood cells mobilized by treatment with rhG-CSF alone. One group of baboons was administered low-dose rhSCF (25 micrograms/kg/d) plus rhG-CSF (100 micrograms/kg/d) while a second group received rhG-CSF alone (100 micrograms/kg/d). Each animal underwent a single 2-hour leukapheresis occurring the day when the number of progenitor cells per volume of blood was maximal. For baboons administered low-dose rhSCF plus rhG-CSF, the leukapheresis products contained 1.8-fold more mononuclear cells and 14.0-fold more progenitor cells compared to the leukapheresis products from animals treated with rhG-CSF alone. All animals successfully engrafted after transplantation of cryopreserved autologous blood cells. In animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells, we observed a time to a platelet count of > 20,000 was 8 days +/- 0, to a white blood cell count (WBC) of > 1,000 was 11 +/- 1 days, and to an absolute neutrophil count (ANC) of > 500 was 12 +/- 1 days. These results compared with 42 +/- 12, 16 +/- 1, and 24 +/- 4 days to achieve platelets > 20,000, WBC > 1,000, and ANC > 500, respectively, for baboons transplanted with rhG-CSF mobilized blood cells. Animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells had blood counts equivalent to pretransplant values within 3 weeks after transplant. The results suggest that the combination of low-dose rhSCF plus rhG-CSF mobilizes greater numbers of progenitor cells that can be collected by leukapheresis than does rhG-CSF alone, that blood cells mobilized by low-dose rhSCF plus rhG-CSF contain marrow repopulating cells, and finally that using a single 2-hour leukapheresis to collect cells, the blood cells mobilized by low-dose rhSCF plus rhG-CSF engraft lethally irradiated recipients more rapidly than do blood cells mobilized by rhG-CSF alone.
我们之前已经表明，给狒狒注射低剂量重组人干细胞因子（rhSCF）加重组人粒细胞集落刺激因子（rhG-CSF），与单独注射rhG-CSF相比，能使血液中动员出更多数量的祖细胞。本研究的目的是确定在接受低剂量rhSCF加rhG-CSF注射的非人灵长类动物的血液中是否存在骨髓重建细胞，如果存在，这些细胞在移植到接受致死性照射的受体中时，是否能像单独用rhG-CSF治疗动员的血细胞一样快速植入。一组狒狒接受低剂量rhSCF（25微克/千克/天）加rhG-CSF（100微克/千克/天），而另一组仅接受rhG-CSF（100微克/千克/天）。每只动物在每单位体积血液中祖细胞数量达到最大值的当天进行一次2小时的白细胞分离术。对于接受低剂量rhSCF加rhG-CSF的狒狒，白细胞分离术产物中的单核细胞数量比单独接受rhG-CSF治疗的动物的白细胞分离术产物多1.8倍，祖细胞数量多14.0倍。所有动物在移植冷冻保存的自体血细胞后均成功植入。在移植低剂量rhSCF加rhG-CSF动员的血细胞的动物中，我们观察到血小板计数>20,000的时间为8天±0天，白细胞计数（WBC）>1,000的时间为11±1天，绝对中性粒细胞计数（ANC）>500的时间为12±1天。相比之下，移植rhG-CSF动员的血细胞的狒狒达到血小板>20,000、WBC>1,000和ANC>500的时间分别为42±12天、16±1天和24±4天。移植低剂量rhSCF加rhG-CSF动员的血细胞的动物在移植后3周内血细胞计数恢复到移植前水平。结果表明，低剂量rhSCF加rhG-CSF联合使用比单独使用rhG-CSF能动员出更多可通过白细胞分离术采集的祖细胞，低剂量rhSCF加rhG-CSF动员的血细胞含有骨髓重建细胞，最后，通过单次2小时白细胞分离术采集细胞时，低剂量rhSCF加rhG-CSF动员的血细胞比单独用rhG-CSF动员的血细胞能更快地植入接受致死性照射的受体。
