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短期给予粒细胞集落刺激因子(G-CSF)对正常供者骨髓和外周血中造血祖细胞数量及克隆形成效率的影响。

The effect of short G-CSF administration on the numbers and clonogenic efficiency of hematopoietic progenitor cells in bone marrow and peripheral blood of normal donors.

作者信息

Zaucha J M, Knopińska-Posłuszny W, Bieniaszewska M, Myśliwski A, Hellmann A

机构信息

Department of Haematology, Medical University, Gdańsk, Poland.

出版信息

Ann Transplant. 2000;5(4):20-6.

Abstract

We have analysed the cellularity, the number of clonogenic cells and their clonogenic efficiency (the number of clonogenic cells/2 x 10(5) MNC) in peripheral blood (PB) and bone marrow (BM) during and after filgrastim (rhG-CSF) mobilization of CD34+ cells in 12 healthy donors for allogeneic stem cell donation. G-CSF was administrated subcutaneously for 5 consecutive days at a dose of 10 micrograms/kg/day. WBC, MNC, CD34+ cell counts, CFU-GM and BFU-E assays in PB were performed at baseline and then daily 12 hours after each G-CSF dose. BM was assayed before start (day 1) and after the last dose (day 6) of G-CSF. Results are given as medians, with ranges in parentheses. In PB the total WBC and MNC increased 7.4-fold (6.0-12.3) and 3.3-fold (1.5-9.4), respectively, reaching a peak of 49.4 x 10(9)/l (32.5-66.6) on day 6 for WBC and 6.28 x 10(9)/l (4.7-13.3) for MNC on day 5. CD34+ cell number reached a peak value of 48.0 x 10(6)/l (45.6-285) on day 6 whereas CFU-GM and BFU-E reached their peaks on day 5, 0.95 x 10(4)/ml (0.05-6.08) and 1.04 x 10(4)/ml, respectively. CFU-MIX, not detectable at baseline, reached a peak of 0.95 x 10(4)/ml (0.006-0.51) on day 5 as well. This was accompanied by an increase in CFU-GM, BFU-E and CFU-MIX clonogenic efficiency: 23-fold (3-150), 9.75-fold (2.2-27.8) and 20-fold (2.5-210), respectively. In BM the total WBC number increased 2.5-fold (1.3-4.9) from the baseline value of 52.6 x 10(9)/l (7.9-137.0) whereas the MNC count increased 2.0-fold (0.81-3.7) from a baseline of 13.6 x 10(9)/l (3.5-54.8). This was, however, not significant. The number of CD34+ cells increased significantly 2.9-fold (0.8-8.3). In 8 donors CFU-MIX were detectable before but not after G-CSF treatment. A similar decrease in CFU-GM and BFU-E clonogenic efficiency occurred but was not significant. CFU-GM and BFU-E numbers did not change. We conclude that the total body numbers of lineage committed progenitors increased during G-CSF administration, which indicate their proliferation in addition to mobilization. The effect of G-CSF on the number of more primitive progenitors in BM is less clear and needs further investigation.

摘要

我们分析了12名健康供体在使用非格司亭(重组人粒细胞集落刺激因子,rhG-CSF)动员CD34+细胞用于异基因干细胞捐献期间及之后外周血(PB)和骨髓(BM)中的细胞密度、克隆形成细胞数量及其克隆形成效率(克隆形成细胞数量/2×10⁵单个核细胞)。G-CSF以10微克/千克/天的剂量连续皮下注射5天。在基线时以及每次G-CSF给药后12小时每日对外周血中的白细胞、单个核细胞、CD34+细胞计数、粒-巨噬细胞集落形成单位(CFU-GM)和爆式红系集落形成单位(BFU-E)进行检测。在G-CSF开始给药前(第1天)和最后一剂给药后(第6天)对骨髓进行检测。结果以中位数表示,括号内为范围。在外周血中,白细胞总数和单个核细胞分别增加了7.4倍(6.0 - 12.3)和3.3倍(1.5 - 9.4),白细胞在第6天达到峰值49.4×10⁹/升(32.5 - 66.6),单个核细胞在第5天达到峰值6.28×10⁹/升(4.7 - 13.3)。CD34+细胞数量在第6天达到峰值48.0×10⁶/升(45.6 - 285),而CFU-GM和BFU-E在第5天达到峰值,分别为0.95×10⁴/毫升(0.05 - 6.08)和1.04×10⁴/毫升。混合集落形成单位(CFU-MIX)在基线时不可检测,在第5天也达到峰值0.95×10⁴/毫升(0.006 - 0.51)。这伴随着CFU-GM、BFU-E和CFU-MIX克隆形成效率的增加:分别为23倍(3 - 150)、9.75倍(2.2 - 27.8)和20倍(2.5 - 210)。在骨髓中,白细胞总数从基线值52.6×10⁹/升(7.9 - 137.0)增加了2.5倍(1.3 - 4.9),而单个核细胞计数从基线13.6×10⁹/升(3.5 - 54.8)增加了2.0倍(0.81 - 3.7)。然而,这并不显著。CD34+细胞数量显著增加了2.9倍(0.8 - 8.3)。在8名供体中,CFU-MIX在G-CSF治疗前可检测到,但治疗后不可检测。CFU-GM和BFU-E克隆形成效率出现了类似的下降,但不显著。CFU-GM和BFU-E的数量没有变化。我们得出结论,在G-CSF给药期间,定向祖细胞的全身数量增加,这表明除了动员外它们还发生了增殖。G-CSF对骨髓中更原始祖细胞数量的影响尚不清楚,需要进一步研究。

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