Liles W Conrad, Broxmeyer Hal E, Rodger Elin, Wood Brent, Hübel Kai, Cooper Scott, Hangoc Giao, Bridger Gary J, Henson Geoffrey W, Calandra Gary, Dale David C
Department of Medicine, University of Washington, HSB AA-522, Box 356422, Seattle, WA 98195.
Blood. 2003 Oct 15;102(8):2728-30. doi: 10.1182/blood-2003-02-0663. Epub 2003 Jul 10.
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 CXCR4 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 microsubcutaneously), 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/microL to 20.7 +/- 3.5/microL at 6 hours. Subsequent dose-response studies showed a maximum increase in circulating CD34+ cells from 2.6 +/- 0.3/microL to 40.4 +/- 3.4/microL at 9 hours after 240 micro/kg AMD3100. Serial administration of AMD3100 (80 microg/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.
基质细胞衍生因子1（SDF1/CXCL12）及其同源受体CXCR4在CD34+细胞迁移中起关键调节作用。我们研究了选择性CXCR4拮抗剂AMD3100是否能动员健康人类志愿者骨髓中的造血祖细胞进入外周血。最初，10名受试者每人皮下注射单剂量AMD3100（80微克），这导致迅速的全身性白细胞增多，同时外周血CD34+细胞增加，通过体外集落形成单位测定，这些细胞代表多能造血祖细胞，6小时时从3.8±0.5/微升增至20.7±3.5/微升。随后的剂量反应研究表明，240微克/千克AMD3100给药后9小时，循环CD34+细胞最多可从2.6±0.3/微升增至40.4±3.4/微升。连续给予AMD3100（80微克/千克/天，共3天）导致外周血CD34+细胞持续、可逆地增加。AMD3100耐受性良好，仅引起轻微、短暂的毒性。这些发现提示AMD3100在造血干细胞移植中用于CD34+细胞动员和采集具有潜在的临床应用价值。
