Aquitaine-Limousin Branch of French Blood Institute and the University Victor Segalen Bordeaux 2, Bordeaux, France.
Transfusion. 2010 Jan;50(1):120-7. doi: 10.1111/j.1537-2995.2009.02436.x. Epub 2009 Oct 12.
The classification of patients into "good" or "poor" mobilizers is based on CD34+ cell count in their peripheral blood (PB) after granulocyte-colony-stimulating factor (G-CSF) injection. We hypothesized that, apart from their mobilization from marrow to the blood, the response to G-CSF of CD34+ cells also includes activation of proliferation, metabolic activity, and proliferative capacity.
Mobilized PB CD34+ cells purified from samples obtained by cytapheresis of multiple myeloma or non-Hodgkin's lymphoma patients of both good (>50 CD34+ cells/microL) and poor (< or =50 CD34+ cells/microL) mobilizers were studied. The initial cell cycle state of CD34+ cells after selection and their kinetics of activation (exit from G(0) phase) during ex vivo culture were analyzed. Their proliferative capacity was estimated on the basis of ex vivo generation of total cells, CD34+ cells, and colony-forming cells (CFCs), in a standardized expansion culture. Indirect insight in metabolic activity was obtained on the basis of their survival (viability and apoptosis follow-up) during the 7-day-long conservation in hypothermia (4 degrees C) in the air or in atmosphere containing 3% O(2)/6% CO(2).
CD34+ cells obtained from good mobilizers were in lower proportion in the G(0) phase, their activation in a cytokine-stimulated culture was accelerated, and they exhibited a lower ex vivo expansion efficiency than those from poor mobilizers. The resistance to hypothermia of good immobilizers' CD34+ cells is impaired.
A good response to G-CSF mobilization treatment is associated with a higher degree of proliferative and metabolic activation of mobilized CD34+ cells with a decrease in their expansion capacity.
根据粒细胞集落刺激因子(G-CSF)注射后外周血(PB)中 CD34+细胞计数,将患者分为“良好”或“不良”动员者。我们假设,除了从骨髓动员到血液之外,CD34+细胞对 G-CSF 的反应还包括增殖、代谢活性和增殖能力的激活。
从多发性骨髓瘤或非霍奇金淋巴瘤患者通过细胞分离术获得的 PB CD34+细胞中纯化出良好(>50 CD34+细胞/μL)和不良(<=50 CD34+细胞/μL)动员者的动员 PB CD34+细胞。分析了选择后 CD34+细胞的初始细胞周期状态及其在体外培养过程中的激活动力学(退出 G0 期)。根据在标准化扩展培养中产生的总细胞、CD34+细胞和集落形成细胞(CFC),估计了它们的增殖能力。通过在 4°C 低温下在空气中或在含有 3%O2/6%CO2 的大气中保存 7 天期间的存活(后续进行活力和凋亡检测),间接了解代谢活性。
来自良好动员者的 CD34+细胞处于 G0 期的比例较低,在细胞因子刺激的培养中激活加快,并且体外扩增效率低于来自不良动员者的 CD34+细胞。良好固定者 CD34+细胞对低温的抵抗力受损。
对 G-CSF 动员治疗的良好反应与动员 CD34+细胞的增殖和代谢激活程度更高相关,同时其扩增能力降低。