Croockewit A J, Raymakers R A, Smeets M E, vd Bosch G, Pennings A H, de Witte T J
Department of Haematology, University Hospital Nijmegen, The Netherlands.
Leukemia. 1998 Apr;12(4):571-7. doi: 10.1038/sj.leu.2400981.
Mobilized peripheral blood progenitor cells (PBPC) have been shown to differ qualitatively from bone marrow (BM) progenitors. The released progenitor cells are predominantly in G0/G1 and show a relatively high percentage of rhodamine dull cells. Within the BM these last two features are characteristic of the more primitive progenitors. Although the mobilized PB cells can give rise to long-term repopulation and thus contain stem cells, the frequency of stem cells is not much higher if long-term initiating cell (LTC-IC) assays are used. To determine whether quiescent stem cells are selectively released or the low-cycle status of PB progenitors is related to the release from the BM microenvironment, the cell cycle status and rhodamine content in the PB and BM during mobilization were studied and compared with steady-state BM. More differentiated and more primitive progenitors were separated based on differentiation markers and cloned in single cell assay. In mobilized PB 54% of the CD34+ cells (n=5) were rhodamine dull compared to 22% in steady-state BM (P=0.014) [n=6]. The percentage of CD34+ cells in the S/G2M phases of the cell cycle was 2.1% in the mobilized PB (n=11), and 18% in steady-state BM (n=11) [P=0.002]. During mobilization the fraction of cells in the S/G2M phase of the cell cycle was 16% in BM (n=7), similar to steady-state BM (P=0.34). The released progenitors represented a selection of BM progenitors, with significantly more primitive progenitors (CD34+/13+/33dim) and less lymphoid precursors (CD34+/19+). Within the more differentiated CD34+113+/33bright, myelomonocytic precursors, both in PB as well as in BM, the percentage S/G2M was relatively higher than in the CD34+/13+/33dim subfraction: in normal BM: median 18% vs 8% (P=0.006) [n=8]; in mobilized PB 3% vs 2% (P=0.03) [n=10]; and in BM during mobilization 24% vs 7% (P=0.01) [n=6]. The cycle status of mobilized PB progenitors was low both in the primitive and more differentiated subfractions. During the mobilization period the BM progenitors are cycling as in steady-state BM. The low-cycle status of the mobilized PB progenitors may be related to the loss of contact with the micro-environment.
已证明动员的外周血祖细胞（PBPC）在质量上与骨髓（BM）祖细胞不同。释放的祖细胞主要处于G0/G1期，并且罗丹明淡染细胞的比例相对较高。在骨髓中，后两个特征是更原始祖细胞的特征。尽管动员的PB细胞可以实现长期重建，因此含有干细胞，但如果使用长期起始细胞（LTC-IC）测定法，干细胞的频率并不会高太多。为了确定静止干细胞是否被选择性释放，或者PB祖细胞的低周期状态是否与从BM微环境中的释放有关，研究了动员期间PB和BM中的细胞周期状态和罗丹明含量，并与稳态BM进行了比较。根据分化标志物分离出更分化和更原始的祖细胞，并在单细胞测定中进行克隆。在动员的PB中，54%的CD34+细胞（n = 5）罗丹明淡染，而稳态BM中为22%（P = 0.014）[n = 6]。动员的PB中处于细胞周期S/G2M期的CD34+细胞百分比为2.1%（n = 11），稳态BM中为18%（n = 11）[P = 0.002]。在动员期间，BM中处于细胞周期S/G2M期的细胞比例为16%（n = 7），与稳态BM相似（P = 0.34）。释放的祖细胞代表了BM祖细胞的一个选择，其中原始祖细胞（CD34+/13+/33dim）明显更多，淋巴样前体细胞（CD34+/19+）更少。在PB和BM中更分化的CD34+113+/33bright髓单核细胞前体中，S/G2M的百分比相对高于CD34+/13+/33dim亚组分：在正常BM中：中位数为18%对8%（P = 0.006）[n = 8]；在动员的PB中为3%对2%（P = 0.03）[n = 10]；在动员期间的BM中为24%对7%（P = 0.01）[n = 6]。动员的PB祖细胞在原始和更分化的亚组分中的周期状态都很低。在动员期间，BM祖细胞像在稳态BM中一样进行细胞周期循环。动员的PB祖细胞的低周期状态可能与与微环境失去接触有关。
