Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist
Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist
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DOI：
10.1182/blood-2003-02-0663
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发表时间：
2003-10-15
期刊：
影响因子：
20.3
通讯作者：
Dale, DC
中科院分区：
文献类型：
--
作者：
Liles, WC;Broxmeyer, HE;Dale, DC
基质细胞衍生因子1（SDF 1/CXCL 12）及其同源受体CXCR 4在CD 34（+）细胞运输中发挥关键调节作用。我们研究了选择性CXCR 14拮抗剂AMD 3100是否可以动员健康志愿者的造血祖细胞从骨髓到外周血。最初，10名受试者每人接受单次剂量的AMD 3100（80 μ g/kg皮下注射），其诱导快速、全身性白细胞增多，与外周血CD 34（+）细胞（通过体外集落形成单位测定代表多能造血祖细胞）增加相关，在6小时时从3.8 +/- 0.5/穆尔增加至20.7 +/- 3.5/穆尔。随后的剂量反应研究显示，240 mug/kg AMD 3100给药后9小时，循环CD 34（+）细胞从2.6 +/- 0.3/穆尔最大增加至40.4 +/- 3.4/穆尔。连续给予AMD 3100（80 μ g/kg/d，持续3天）导致外周血CD 34（+）细胞持续可逆性增加。AMD 3100耐受性良好，仅引起轻度、一过性毒性。这些结果表明，AMD 3100在造血干细胞移植中动员和收集CD 34（+）细胞方面具有潜在的临床应用价值。(C)2003年，美国血液学会。
Stromal cell-derived factor 1 (SDF1/CXCL12 ) and its cognate receptor, CXCR4, play key regulatory roles in CD34(+) cell trafficking. We investigated whether AMD3100, a selective CXCR14 antagonist, could mobilize hematopoietic progenitor cells from marrow to peripheral blood in healthy human volunteers. Initially, 10 persons each received a single dose of AMD3100 (80 mug/kg subcutaneously), which induced rapid, generalized leukocytosis associated with an increase in peripheral blood CD34(+) cells, representing pluripotent hematopoietic progenitors by in vitro colony-forming unit assays, from 3.8 +/- 0.5/muL to 20.7 +/- 3.5/muL at 6 hours. Subsequent dose-response studies showed a maximum increase in circulating CD34(+) cells from 2.6 +/- 0.3/muL to 40.4 +/- 3.4/muL at 9 hours after 240 mug/kg AMD3100. Serial administration of AMD3100 (80 mug/kg/d for 3 days) resulted in consistent, reversible increases in peripheral blood CD34(+) cells. AMD3100 was well tolerated and caused only mild, transient toxicity. These findings suggest potential clinical application of AMD3100 for CD34(+) cell mobilization and collection for hematopoietic stem cell transplantation. (C) 2003 by The American Society of Hematology.