Catani L, Gugliotta L, Campanini E, Mangianti S, Gibellini D, Baravelli S, Vianelli N, Lemoli R M, Tura S
Istituto di Ematologia e Oncologia Medica L. e A. Seràgnoli, University of Bologna, Italy.
Br J Haematol. 1998 Jan;100(1):207-18. doi: 10.1046/j.1365-2141.1998.00511.x.
In the present study we investigated the proliferative response of megakaryocyte progenitor cells (CFU-MK) derived from peripheral blood stem cell (PBSC) collections of patients with haematological malignancies and normal donors. Highly purified CD34+ cells and mononuclear cell fractions were assayed in the presence of recombinant interleukin-3 (IL-3) and pegylated-recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), alone or in combination, and megakaryocyte colony formation was evaluated in the plasma clot. In comparison, steady-state bone marrow samples from normal donors were highly enriched in CD34+ cells and tested with the cytokines studied. Our results showed that IL-3 was able to stimulate CFU-MK colony formation from bone marrow and peripheral blood CD34+ cells. Similarly, PEG-rHuMGDF stimulated, in a dose-response manner, CD34+ cells from the bone marrow. However, normal mobilized peripheral blood CD34+ cells were not induced to generate CFU-MK colonies by PEG-rHuMGDE The same lack of response was observed when patients peripheral blood CD34+ cells primed with chemotherapy plus G-CSF or with G-CSF alone were assessed. In contrast, PEG-rHuMGDF stimulated CFU-MK growth when mononuclear cells, either from the bone marrow or from mobilized peripheral blood, were grown in plasma clot. Moreover, we analysed by flow cytometry the expression of Mpl receptor on the cell membrane of normal mobilized peripheral blood and normal steady-state bone marrow CD34+ cells. Our results showed a reduced expression of Mpl receptor on mobilized peripheral blood progenitor cells in comparison with bone marrow cells.
在本研究中，我们调查了血液系统恶性肿瘤患者和正常供体外周血干细胞（PBSC）采集物中巨核细胞祖细胞（CFU-MK）的增殖反应。在重组白细胞介素-3（IL-3）和聚乙二醇化重组人巨核细胞生长和发育因子（PEG-rHuMGDF）单独或联合存在的情况下，对高度纯化的CD34+细胞和单核细胞组分进行检测，并在血浆凝块中评估巨核细胞集落形成。相比之下，来自正常供体的稳态骨髓样本中CD34+细胞高度富集，并使用所研究的细胞因子进行检测。我们的结果表明，IL-3能够刺激骨髓和外周血CD34+细胞形成CFU-MK集落。同样，PEG-rHuMGDF以剂量反应方式刺激来自骨髓的CD34+细胞。然而，聚乙二醇化重组人巨核细胞生长和发育因子（PEG-rHuMGDE）并未诱导正常动员外周血CD34+细胞生成CFU-MK集落。当评估用化疗加粒细胞集落刺激因子（G-CSF）或仅用G-CSF预处理的患者外周血CD34+细胞时，也观察到相同的无反应情况。相比之下，当来自骨髓或动员外周血的单核细胞在血浆凝块中生长时，PEG-rHuMGDF刺激CFU-MK生长。此外，我们通过流式细胞术分析了正常动员外周血和正常稳态骨髓CD34+细胞膜上Mpl受体的表达。我们的结果表明，与骨髓细胞相比，动员外周血祖细胞上Mpl受体的表达降低。
