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用于治疗心碎综合征的干细胞疗法:微型器官移植

Stem cell therapy for the broken heart: mini-organ transplantation.

作者信息

Mansour S, Roy D C, Lemieux B, Ouellet C, Stevens L-M, Noiseux N

机构信息

Cardiology Department, Hôtel-Dieu de Montréal, Centre Hospitalier de L'Université de Montréal, Québec H2W 1T8, Canada.

出版信息

Transplant Proc. 2009 Oct;41(8):3353-7. doi: 10.1016/j.transproceed.2009.08.033.

DOI:10.1016/j.transproceed.2009.08.033
PMID:19857748
Abstract

BACKGROUND

Myocardial infarction (MI) is characterized by irreversible loss of cardiomyocytes, resulting in impaired ventricular function. Stem cell therapy using autologous progenitor cells has emerged as a promising approach. Experimental studies have demonstrated that highly selected hematopoeitic stem cells, which are characterized by the presence of the surface markers CD34 and CD133, may contribute to repair of the acutely infarcted myocardium by inducing neovascularization, inhibiting apoptosis, and promoting cardiomyogenesis. We sought, to evaluate the intracoronary injection of CD133+ stem cells for cardiac repair in patients with dysfunctional myocardium after an acute MI.

PATIENTS AND METHODS

In this Canadian randomized, double-blind, placebo-controlled, Phase I-II study ("COMPARE-AMI"), we are evaluating the feasibility, safety, and efficacy of intracoronary injection of selected CD133+ stem cells for cardiac repair in patients with impaired cardiac function after successfully stented acute MI. Since November 2007, we have enrolled 14 patients in the study. Their mean age was 50.5 +/- 9.1 years, including 93% men. The culprit lesion was always on the left anterior descending artery (LAD). Their maximum troponin and CKMB levels were 8.4 +/- 6.1 microg/L and 322 +/- 225 U/L, respectively.

RESULTS

Compared with the baseline, we observed a significant 8.7% improvement in left ventricular ejection fraction at 4 months follow-up, namely, from 41.3 +/- 5.5% to 50.0 +/- 8.2% (n = 7; P = .008). There were no protocol-related complications. Our trial is designed to recruit 40 patients who are randomized 1:1 to receive CD133+ cells or placebo.

PERSPECTIVE

There is a need to seek out new therapeutics for the treatment of ischemic heart disease addressing the early loss of viable myocytes. Stem cell transplantation has shown early promise; this appraisal needs well-designed, controlled studies.

摘要

背景

心肌梗死(MI)的特征是心肌细胞发生不可逆性丧失,从而导致心室功能受损。使用自体祖细胞的干细胞疗法已成为一种有前景的治疗方法。实验研究表明,以表面标志物CD34和CD133的存在为特征的高度选择的造血干细胞,可能通过诱导新生血管形成、抑制细胞凋亡和促进心肌生成,有助于急性梗死心肌的修复。我们试图评估冠状动脉内注射CD133+干细胞对急性心肌梗死后心肌功能不全患者心脏修复的作用。

患者和方法

在这项加拿大的随机、双盲、安慰剂对照的I-II期研究(“COMPARE-AMI”)中,我们正在评估冠状动脉内注射选择的CD133+干细胞对成功置入支架的急性心肌梗死后心脏功能受损患者进行心脏修复的可行性、安全性和有效性。自2007年11月以来,我们已招募了14名患者参与该研究。他们的平均年龄为50.5±9.1岁,其中男性占93%。罪犯病变总是位于左前降支(LAD)。他们的肌钙蛋白和肌酸激酶同工酶(CKMB)的最高水平分别为8.4±6.1μg/L和322±225U/L。

结果

与基线相比,在4个月的随访中,我们观察到左心室射血分数有显著的8.7%的改善,即从41.3±5.5%提高到50.0±8.2%(n = 7;P = 0.008)。没有与方案相关的并发症。我们的试验旨在招募40名患者,他们被随机分为1:1接受CD133+细胞或安慰剂。

前景

需要寻找新的治疗方法来治疗缺血性心脏病,解决存活心肌细胞的早期丧失问题。干细胞移植已显示出早期的前景;这种评估需要精心设计的对照研究。

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