Tjønnfjord G E, Steen R, Evensen S A, Thorsby E, Egeland T
Institute of Transplantation Immunology National Hospital, University of Oslo, Norway.
Blood. 1994 Oct 15;84(8):2795-801.
Primed peripheral blood hematopoietic stem cells (PBSC) generate and sustain lymphohematopoiesis in myeloablated animals, and recent reports indicate that allogeneic transplantation using PBSC grafts may be feasible in humans. A major concern with the use of PBSC transplants is that permanent engraftment may be limited because of lack of sufficient numbers of primitive progenitor cells in the graft. In the present study, in vitro colony formation and immunophenotype of CD34+ cells in PB of healthy adults during short-term granulocyte colony-stimulating factor (G-CSF) administration were compared with that of CD34+ cells in normal bone marrow (BM). The number of CD34+ cells mobilized to PB peaked at day 4 or 5 of G-CSF administration. The phenotypic profile of CD34+ PB cells showed a substantial increase in the percentage of CD34+CD13+ and CD34+CD33+ cells (myeloid progenitors) and a corresponding decrease in the percentage of CD34+CD10+ and CD34+CD19+ cells (B lymphoid progenitors) compared with CD34+ BM cells. The other subsets studied, including CD34+CD38- and CD34+HLA-DR- cells, were present in both compartments in similar proportions. Furthermore, primed CD34+ PB cells were enriched for colony-forming cells (CFC) and displayed an increased clonogenicity when compared with their counterparts in BM. A comparison between a postulated PBSC graft and an average BM graft is presented, showing that such PBSC grafts will be enriched for CD34+ cells as a whole, CD34+CD33+ cells, and colony-forming cells (CFC), factors which have been shown to correlate to acceleration of hematologic reconstitution and reduction in requirements for supportive care in autografting. Hence, we predict that allogeneic transplantation using G-CSF-primed PBSC grafts will result in a more rapid hematologic reconstitution after myeloablative conditioning than BM grafting. The question of whether PBSC allografting will result in permanent engraftment and clinical benefits as observed in autografting has to be determined in prospective clinical studies.
经动员的外周血造血干细胞(PBSC)可在接受清髓的动物体内产生并维持淋巴细胞生成和造血,近期报告表明,使用PBSC移植物进行同种异体移植在人类中可能是可行的。使用PBSC移植的一个主要担忧是,由于移植物中缺乏足够数量的原始祖细胞,永久植入可能会受到限制。在本研究中,将健康成年人在短期使用粒细胞集落刺激因子(G-CSF)期间外周血中CD34+细胞的体外集落形成和免疫表型与正常骨髓(BM)中的CD34+细胞进行了比较。动员至外周血的CD34+细胞数量在G-CSF给药的第4天或第5天达到峰值。与CD34+骨髓细胞相比,CD34+外周血细胞的表型特征显示CD34+CD13+和CD34+CD33+细胞(髓系祖细胞)的百分比大幅增加,而CD34+CD10+和CD34+CD19+细胞(B淋巴系祖细胞)的百分比相应下降。所研究的其他亚群,包括CD34+CD38-和CD34+HLA-DR-细胞,在两个区室中的比例相似。此外,与骨髓中的对应细胞相比,经动员的CD34+外周血细胞富含集落形成细胞(CFC),且克隆形成能力增强。本文对假定的PBSC移植物与平均骨髓移植物进行了比较,结果表明,此类PBSC移植物总体上富含CD34+细胞、CD34+CD33+细胞和集落形成细胞(CFC),这些因素已被证明与加速血液学重建以及减少自体移植中支持治疗的需求相关。因此,我们预测,使用经G-CSF动员的PBSC移植物进行同种异体移植,在清髓预处理后将比骨髓移植导致更快的血液学重建。PBSC同种异体移植是否会像自体移植那样导致永久植入并带来临床益处,这一问题必须在前瞻性临床研究中加以确定。