Andrews R G, Bensinger W I, Knitter G H, Bartelmez S H, Longin K, Bernstein I D, Appelbaum F R, Zsebo K M
Program in Pediatric Oncology, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Blood. 1992 Dec 1;80(11):2715-20.
Recombinant human stem cell factor (SCF), the ligand for c-kit, has been shown to stimulate increased numbers of hematopoietic progenitor cells of multiple types to circulate in the blood of baboons, but it was not known if the cells stimulated to circulate by SCF contained cells capable of engrafting and rescuing lethally irradiated baboons. Peripheral blood mononuclear cells (PBMNC) were collected by leukapheresis from four untreated control baboons and from three baboons on the 10th or 11th day of treatment with SCF (200 micrograms/kg/d). All animals were transplanted with 1.00 to 1.04 x 10(8)/kg of cryopreserved autologous PBMNC after treatment with a single dose of 1,020 cGy total body irradiation (TBI). Three animals were transplanted with PBMNC that had been collected during SCF treatment, 24 to 38 days after the last dose of SCF. Rapid trilineage engraftment was documented by bone marrow biopsy in all three. The mean time to a total white blood cell count (WBC) > or = 500/microL, WBC > or = 1,000/microL, and an absolute neutrophil count (ANC) > or = 500/microL was 15 +/- 3 (mean +/- SD), 19 +/- 1, and 19 +/- 2 days, respectively. Two animals remain alive with stable engraftment more than 180 and 245 days posttransplant. The third died of sepsis 32 days posttransplant with a hypercellular marrow showing trilineage engraftment. The surviving animals were transfusion independent by 10 and 59 days posttransplant. Four control animals were transplanted with PBMNC collected in the absence of SCF stimulation. One was treated for 11 days with SCF (200 micrograms/kg/d) after PBMNC were collected. This animal was transplanted 25 days after the last dose of SCF. None of the four control animals engrafted and they died 13, 16, 28, and 38 days posttransplant with marrow aplasia. Treatment with SCF stimulates the circulation of cells that engraft and rescue lethally irradiated baboons. The characteristics of the transplantable cells present in the circulation are now amenable to direct study.
重组人干细胞因子（SCF）是c - kit的配体，已被证明能刺激多种造血祖细胞数量增加，使其在狒狒血液中循环，但尚不清楚经SCF刺激而循环的细胞中是否包含能够植入并拯救受到致死性照射的狒狒的细胞。通过白细胞分离术从4只未经处理的对照狒狒以及3只在接受SCF（200微克/千克/天）治疗的第10天或第11天的狒狒中采集外周血单个核细胞（PBMNC）。在用单剂量1020 cGy全身照射（TBI）处理后，所有动物均接受1.00至1.04×10⁸/千克的冷冻保存自体PBMNC移植。3只动物接受了在SCF治疗期间（最后一剂SCF后24至38天）采集的PBMNC移植。通过骨髓活检证实所有3只动物均迅速出现三系造血植入。白细胞总数（WBC）≥500/微升、WBC≥1000/微升以及绝对中性粒细胞计数（ANC）≥500/微升的平均时间分别为15±3（均值±标准差）天、19±1天和19±2天。2只动物在移植后180多天和245多天仍存活且植入稳定。第三只动物在移植后32天死于败血症，其骨髓细胞增多，显示三系造血植入。存活的动物在移植后10天和59天不再依赖输血。4只对照动物接受了在无SCF刺激情况下采集的PBMNC移植。其中1只在采集PBMNC后接受了11天的SCF（200微克/千克/天）治疗。这只动物在最后一剂SCF后25天接受移植。4只对照动物均未实现植入，它们在移植后13天、16天、28天和38天死于骨髓再生障碍。SCF治疗可刺激能够植入并拯救受到致死性照射的狒狒的细胞进行循环。现在可以直接研究循环中存在的可移植细胞的特性。
