Yan X Q, Hartley C, McElroy P, Chang A, McCrea C, McNiece I
Department of Developmental Hematology, Amgen Inc, Thousand Oaks, CA 91320-1789, USA.
Blood. 1995 May 1;85(9):2303-7.
Mobilized peripheral blood progenitor cells (PBPC) have been shown to provide rapid engraftment in patients given high-dose chemotherapy. PBPC contain cells with long-term engraftment potential as shown in animal models. In this study we have further analyzed mobilized PBPC for their ability to support serial transplantation of irradiated mice. Transplantation of recombinant human granulocyte colony-stimulating factor (rhG-CSF) plus recombinant rat stem cell factor (rrSCF) mobilized PBPC resulted in 98% donor engraftment of primary recipients at 12 to 14 months post-transplantation. Bone marrow (BM) cells from these primary recipients were harvested and transplanted into secondary recipients. At 6 months posttransplantation, all surviving secondary recipients had donor engraftment. Polymerase chain reaction (PCR) analysis showed greater than 90% male cells in spleens, thymuses, and lymph nodes. Myeloid colonies from BM cells of secondary recipients demonstrated granulocyte/macrophage colony-forming cells (GM-CFC) of male origin in all animals. In comparison, transplantation of rhG-CSF mobilized PBPC resulted in decreased male engraftment in secondary recipients. BM cells from secondary recipients, who originally received PBPC mobilized by the combination of rrSCF and rhG-CSF, were further passaged to tertiary female recipients. At 6 months posttransplantation, 90% of animals had male-derived hematopoiesis by whole-blood PCR analysis. These data showed that PBPC mobilized with rhG-CSF plus rrSCF contained cells that are transplantable and able to maintain hematopoiesis for more than 26 months, suggesting that the mobilized long-term reconstituting stem cells (LTRC) have extensive proliferative potential and resemble those that reside in the BM. In addition, the data demonstrated increased mobilization of LTRC with rhG-CSF plus rrSCF compared to rhG-CSF alone.
已证明动员的外周血祖细胞(PBPC)在接受高剂量化疗的患者中能实现快速植入。如动物模型所示,PBPC含有具有长期植入潜力的细胞。在本研究中,我们进一步分析了动员的PBPC支持经照射小鼠进行连续移植的能力。移植重组人粒细胞集落刺激因子(rhG-CSF)加重组大鼠干细胞因子(rrSCF)动员的PBPC后,在移植后12至14个月,98%的初次受体实现了供体植入。收集这些初次受体的骨髓(BM)细胞并移植到二次受体中。移植后6个月,所有存活的二次受体都实现了供体植入。聚合酶链反应(PCR)分析显示,脾脏、胸腺和淋巴结中雄性细胞比例超过90%。二次受体BM细胞形成的髓系集落显示,所有动物中均有雄性来源的粒细胞/巨噬细胞集落形成细胞(GM-CFC)。相比之下,移植rhG-CSF动员的PBPC导致二次受体中雄性植入减少。最初接受rrSCF和rhG-CSF联合动员的PBPC的二次受体的BM细胞进一步移植到三次雌性受体中。移植后6个月,通过全血PCR分析,90%的动物具有雄性来源的造血功能。这些数据表明,rhG-CSF加rrSCF动员的PBPC含有可移植且能够维持造血功能超过26个月的细胞,这表明动员的长期重建造血干细胞(LTRC)具有广泛的增殖潜力,且与骨髓中存在的干细胞相似。此外,数据表明,与单独使用rhG-CSF相比,rhG-CSF加rrSCF可增加LTRC的动员。