Translational Medicine Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland, USA.
Cytotherapy. 2009;11(8):1016-9. doi: 10.3109/14653240903131640.
Bone marrow (BM)-derived cells may repair cardiovascular injury but populations of interest circulate in small numbers. Cytokines such as granulocyte-colony-stimulating factor mobilize cells under investigation for this purpose, including CD133+ but require injections over multiple days and may promote inflammation. The purpose of this study was to evaluate the effects of a novel CXCR4 inhibitor (plerixafor), previously shown to mobilize CD34+ stem cells, on CD133+ mobilization and markers of inflammation.
Healthy subjects received a single subcutaneous injection of plerixafor in escalating doses: 240 mcg/kg (n = 3), 320 mcg/kg (n = 5) and 400 mcg/kg (n = 7). CD133+ and CD133+/VEGFR-2+ cells were measured by flow cytometry at baseline, then 4-6 h following plerixafor injection. Markers of inflammation in serum were measured at baseline, then again 10 h following injection of the 400 mcg/kg dose.
Across all doses, white blood cells increased on average three-fold from baseline values. CD133+ cells increased on average 24-fold (from 616 +/- 141 cells/mL to 14 713 +/- 4423 cells/mL, P = 0.0064) without clear evidence of a dose effect. CD133+/VEGFR-2+ cells ranged from 0 to 20 cells/mL at baseline and from 0 to 124 cells/mL following plerixafor administration, although the rarity of these cells precluded a statistical analysis of this population. C-reactive protein and serum amyloid type A were not increased after the 400 mcg/kg dose. Pro-inflammatory cytokine levels were undetectable before and after plerixafor, except for macrophage inflammatory protein-1 beta, which increased slightly but significantly after the 400 mcg/kg dose of plerixafor (P = 0.0156).
CD133+ cells are mobilized into the circulation following a single injection of the CXCR4 antagonist plerixafor, without clear evidence for systemic activation of inflammation. This effect may be of importance in cell-based approaches for treating cardiovascular diseases.
骨髓（BM）来源的细胞可能修复心血管损伤，但感兴趣的细胞群体数量较少。粒细胞集落刺激因子等细胞因子可动员用于此目的的细胞，包括 CD133+，但需要多次注射多天，并且可能促进炎症。本研究的目的是评估一种新型 CXCR4 抑制剂（plerixafor）的作用，该抑制剂先前已显示可动员 CD34+干细胞，对 CD133+动员和炎症标志物的影响。
健康受试者接受递增剂量的单次皮下注射 plerixafor：240 mcg/kg（n = 3），320 mcg/kg（n = 5）和 400 mcg/kg（n = 7）。在基线时，然后在 plerixafor 注射后 4-6 小时，通过流式细胞术测量 CD133+和 CD133+/VEGFR-2+细胞。在基线时测量血清中的炎症标志物，然后在注射 400 mcg/kg 剂量后 10 小时再次测量。
在所有剂量下，白细胞平均从基线值增加三倍。CD133+细胞平均增加 24 倍（从 616 +/- 141 个/毫升增加到 14 713 +/- 4423 个/毫升，P = 0.0064），但无明显的剂量效应。CD133+/VEGFR-2+细胞在基线时范围为 0 至 20 个/毫升，在 plerixafor 给药后范围为 0 至 124 个/毫升，尽管这些细胞的稀有性排除了对此人群的统计分析。在注射 400 mcg/kg 剂量后，C-反应蛋白和血清淀粉样蛋白 A 没有增加。在 plerixafor 之前和之后，促炎细胞因子水平均无法检测到，除了巨噬细胞炎症蛋白-1β，在注射 400 mcg/kg 剂量的 plerixafor 后略有但显着增加（P = 0.0156）。
在单次注射 CXCR4 拮抗剂 plerixafor 后，CD133+细胞被动员到循环中，没有明显证据表明全身炎症激活。这种作用可能对基于细胞的治疗心血管疾病的方法很重要。
