Deng Zhengrong, Yang Chun, Deng Huixing, Yang Aimin, Geng Tao, Chen Xinyi, Ma Aiqun, Liu Zhiquan
Department of Cardiology, the First Hospital of Xi'an Jiaotong University, No. 1 Jiankang Road, Xi'an, Shaanxi, 710061, China.
Int J Cardiol. 2006 Oct 26;113(1):92-6. doi: 10.1016/j.ijcard.2006.06.014. Epub 2006 Aug 7.
Stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) has been proposed to improve cardiac function and prevent ventricular remodeling after acute myocardial infarction (AMI) in preclinical and clinical studies. It has been demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) can improve collateral flow in patients with coronary artery disease. In this study, we used GM-CSF to mobilize the bone marrow stem cells (BMSCs) in patients with AMI and assessed the safety, feasibility and efficacy of this treatment.
Twenty patients with AMI were randomly divided into GM-CSF group (10 microg/kg body weight, for 7 days) and control group (saline). The absolute counts of CD34 positive cells in peripheral blood were enumerated with flow cytometry. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrotic factor-alpha (TNF-alpha) were measured on days 1, 3, 7, 10 and 14. Echocardiography (UCG) was done on day 7 and after 12 months.
Peripheral CD34 positive cells in GM-CSF patients obviously increased shortly after using GM-CSF and peaked on day 7 (p<0.01 versus controls). GM-CSF group had significantly higher mean level of plasma CRP than controls on day 10 (p<0.05). The levels of IL-6 and TNF-alpha in therapy patients were as same as in controls. Left ventricular ejection fraction (EF) at 12 months was significantly greater than that on day 7 in GM-CSF patients (p<0.05). The EF in controls had no obvious differences in follow-up. There were no statistically differences regarding the left ventricular end-systolic volume (LVESV), the left ventricular end-diastolic volume (LVEDV) and the resting wall thickening (WT) in the infarct zone in two groups in follow-up.
Our results demonstrate that GM-CSF can effectively mobilize the CD34 positive cells and at the same time may increase the levels of plasma CRP in patients with AMI. The remote effects of this drug need to be further defined.
在临床前和临床研究中，已提出使用粒细胞集落刺激因子（G-CSF）进行干细胞动员，以改善急性心肌梗死（AMI）后的心脏功能并预防心室重构。已证明粒细胞-巨噬细胞集落刺激因子（GM-CSF）可改善冠状动脉疾病患者的侧支血流。在本研究中，我们使用GM-CSF动员AMI患者的骨髓干细胞（BMSCs），并评估该治疗的安全性、可行性和疗效。
20例AMI患者随机分为GM-CSF组（10μg/kg体重，共7天）和对照组（生理盐水）。采用流式细胞术计数外周血中CD34阳性细胞的绝对计数。在第1、3、7、10和14天测量血浆C反应蛋白（CRP）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平。在第7天和12个月后进行超声心动图（UCG）检查。
GM-CSF治疗的患者外周血CD34阳性细胞在使用GM-CSF后不久明显增加，并在第7天达到峰值（与对照组相比，p<0.01）。GM-CSF组在第10天时血浆CRP的平均水平显著高于对照组（p<0.05）。治疗组患者的IL-6和TNF-α水平与对照组相同。GM-CSF治疗的患者在12个月时的左心室射血分数（EF）显著高于第7天时（p<0.05）。对照组的EF在随访中无明显差异。两组随访时梗死区的左心室收缩末期容积（LVESV）、左心室舒张末期容积（LVEDV）和静息壁增厚（WT）无统计学差异。
我们的结果表明，GM-CSF可有效动员AMI患者的CD34阳性细胞，同时可能增加血浆CRP水平。该药物的远期效应有待进一步明确。
