冠状动脉内注射低氧预处理骨髓单个核细胞治疗急性心肌梗死患者的安全性和有效性：中国急性心肌梗死（CHINA-AMI）随机对照试验

Safety and efficacy of intracoronary hypoxia-preconditioned bone marrow mononuclear cell administration for acute myocardial infarction patients: The CHINA-AMI randomized controlled trial.

作者信息

Hu Xinyang, Huang Xin, Yang Qian, Wang Lihua, Sun Jianzhong, Zhan Hongwei, Lin Jianjing, Pu Zhaoxia, Jiang Jun, Sun Yong, Xiang Meixiang, Liu Xianbao, Xie Xiaojie, Yu Xia, Chen Zexin, Tse Hung-Fat, Zhang Jianyi, Wang Jian'an

机构信息

Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.

Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.

出版信息

Int J Cardiol. 2015 Apr 1;184:446-451. doi: 10.1016/j.ijcard.2015.02.084. Epub 2015 Feb 25.

DOI:10.1016/j.ijcard.2015.02.084

PMID:25755063

Abstract

BACKGROUND

Pre-clinical studies have shown that hypoxia preconditioning can enhance stem cell therapeutic potential for myocardial repair. We sought to investigate the safety and feasibility of intracoronary administration of hypoxia-preconditioned bone marrow mononuclear cells (HP-BMCs) for acute ST segment elevation myocardial infarction (STEMI).

METHODS

We randomized 22 patients with acute STEMI to receive intracoronary administration of normoxia bone marrow mononuclear cells (N-BMCs) (n=11) or HP-BMCs (n=11) following successful reperfusion. Another 14 patients receiving standard therapy were recruited as control (n=14).

RESULTS

There were no differences in the occurrence of major adverse cardiovascular events at 30 days and 1 year among three groups. There were significant improvement in the change of left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) in HP-BMC group both at 6 and 12 months compared with N-BMCs or control group (P<0.05). No differences were observed in the change of left ventricular ejection fraction (LVEF), or wall motion score index (WMSI) among three groups. Nevertheless, WMSI was improved in HP-BMCs and N-BMC group (P<0.05, within group), but not in control. The ratio of myocardial perfusion defect determined by SPECT was significantly decreased in HP-BMCs and N-BMC groups at 6months compared with baseline (P<0.05, within group), but no significant differences were observed among three groups.

CONCLUSIONS

Our results provide the first-in-man evidence that intracoronary administration of HP-BMCs following acute MI appears to be safe and feasible. These results provide the basis for future prospective randomized clinical trials in a larger patient cohort.

CLINICAL TRIAL REGISTRATION INFORMATION

NCT01234181 (http://clinicaltrials.gov/ct2/show/NCT01234181?term=NCT01234181&rank=1).

摘要

背景

临床前研究表明，缺氧预处理可增强干细胞对心肌修复的治疗潜力。我们旨在研究冠状动脉内注射缺氧预处理的骨髓单个核细胞（HP-BMCs）治疗急性ST段抬高型心肌梗死（STEMI）的安全性和可行性。

方法

我们将22例急性STEMI患者随机分为两组，在成功再灌注后，一组接受冠状动脉内注射常氧骨髓单个核细胞（N-BMCs，n = 11），另一组接受冠状动脉内注射HP-BMCs（n = 11）。另外招募14例接受标准治疗的患者作为对照组（n = 14）。

结果

三组在30天和1年时主要不良心血管事件的发生率无差异。与N-BMCs组或对照组相比，HP-BMCs组在6个月和12个月时左心室舒张末期容积（LVEDV）和收缩末期容积（LVESV）的变化有显著改善（P<0.05）。三组左心室射血分数（LVEF）或室壁运动评分指数（WMSI）的变化无差异。然而，HP-BMCs组和N-BMCs组的WMSI有所改善（组内P<0.05），而对照组未改善。与基线相比，HP-BMCs组和N-BMCs组在6个月时SPECT测定的心肌灌注缺损比例显著降低（组内P<0.05），但三组之间无显著差异。