Bone marrow stem cell transplantation for improving heart function of patients with acute myocardial infarction: a systematic review

doi:10.3969/j.issn.2095-4344.2014.41.023

Abstract

Abstract:

BACKGROUND: Although increasing studies have shown that autologous bone marrow stem cell transplantation can treat myocardial infarction, but there is a lack of large-scale multi-center randomized controlled trials to illustrate the therapeutic effectiveness of autologous bone marrow stem cell treatment for myocardial infarction.

OBJECTIVE: To systematically evaluate the improvement of heart function in patients with myocardial infarction undergoing autologous bone marrow stem cell transplantation.

METHODS: Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMbase, PEDro (www.pedro.org.au), OpenSIGLE, National Technical Information Service (NTIS), CNKI, VIP database (VlP), Wanfang Data and Chinese biomedical literature database (CBM) were searched for the randomized controlled trials addressing bone marrow stem cell transplantation for heart function in patients with myocardial infarction. The bibliographies of the included studies were also searched. The time span was from database establishment to November 2012. The extracted data were analyzed by RevMan5.1.

RESULTS AND CONCLUSION: A total of 14 randomized controlled trials were included. Results from the meta-analysis showed that the ejection fraction and cardiac output of patients undergoing bone marrow stem cell transplantation was significantly different from those of patients without cell transplantation (WMD=5.23, 95%CI (0.73, 9.72), P < 0.01; WMD=1.69, 95%CI (1.23, 2.16), P < 0.000 01). Current evidence has demonstrated that bone marrow stem cell transplantation can remarkably improve the ejection fraction and cardiac output of myocardial infarction patients, which can be clinically recommended for improvement of heart function. Due to the limitations of the included studies, more large-sample, multi-center high-quality randomized controlled trials are required to further verify the therapeutic methods and effectiveness.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: bone marrow, stem cells, transplantation, autologous, myocardial infarction

CLC Number:

R394.2

Liu Yang, Li Xiao-yan, Chen Pan-pan, Li Jun . Bone marrow stem cell transplantation for improving heart function of patients with acute myocardial infarction: a systematic review[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(41): 6689-6695.

Figures/Tables 3

2.1 纳入研究的一般情况初检出相关文献525篇，其中中文199篇，英文326篇。剔除重复发表及明显不符合纳入标准的文献278篇，经阅读文题和摘要，纳入46篇临床对照研究。进一步查找和阅读全文，排除其中的非随机对照试验和无对照组的临床试验后，最终纳入14篇RCT[3-16]，其中中文9篇[3-11]，英文5篇[12-16]，见表1。 2.2 纳入研究的偏倚风险评价见图1和图2。根据Cochrane协助网推荐的偏倚风险评估方法，在纳入的14项研究中，11项研究随机分组方案明确[3-5，7-9，12-16]，3项研究随机方案不清楚[6，10-11]；14篇文章中未提及是否采用隐蔽分组；1项研究对资料收集和分析人员实施盲法[12]，其他13项研究对资料收集和分析人员是否实施盲法描述不清楚[3-11，13-16]；1项研究对患者实施了盲法[11]；14项研究均报道了完整的结果数据[3-16]；14项研究对选择性报道的描述均不清楚[3-16]。就每项研究而言，Beitnes等[12]为低偏倚风险；Giajek等[13]、Hebots等[14]、Suarezde等[15]、Schachinger等[16]、尹作民等[3]、李晓林等[4]、李长江等[5]、刘品发等[7]、晏凯利等[8]、刘俊等[9]的研究为中偏倚风险；张清队等[6]、刘平等[10]、张宇燕等[11]的研究为高偏倚风险。 2.3 自体骨髓干细胞移植对心肌梗死患者心功能Meta分析 2.3.1 自体骨髓干细胞移植对射血分数的影响用心脏超声来测量患者的心脏射血分数。14项研究均报道了自体骨髓干细胞移植对心肌梗死患者射血分数的影响。因各研究间存在异质性，采用随机效应模式进行分析。结果显示：自体骨髓干细胞治疗后心肌梗死患者的射血分数与常规治疗患者比较，其差异有显著性意义[WMD=5.23，95%CI (0.73，9.72)]，P < 0.01(图3)。敏感性分析剔除刘平、张宇燕、张清队高偏倚风险的文献后，结果差异仍有显著性意义，说明Meta分析结果稳定。漏斗图4不对称，提示可能与阴性结果未发表相关。由于考虑到纳入研究的指标观察时间不甚一致，所以进行了亚组分析，其中有4项研究统计了术后1个月对射血分数的影响，Meta分析结果为[WMD=3.48，95%CI(1.46，5.50)]，P=0.000 7，差异有显著性意义。研究提示其中有7项研究统计了术后6个月对射血分数的影响，Meta分析结果为[WMD=1.65，95%CI(0.22，3.08)]，P=0.03，差异有显著性意义(图5，6)。提示骨髓干细胞移植治疗有利于心肌梗死患者射血分数的改善。 2.3.2 自体骨髓干细胞移植后对心肌梗死患者心输出量的影响有3项研究报道了自体骨髓干细胞移植后对心肌梗死患者心输出量的影响[4，8-9]。因各研究间异质性为0%，采用固定效应模式进行分析。结果显示：自体骨髓干细胞治疗后心肌梗死患者的心输出量与常规治疗的心肌梗死患者比较，其差异有显著性意义[WMD=1.69，95%CI(1.23，2.16)]，P < 0.000 01(图7)。说明骨髓干细胞移植治疗对心输出量的改善强于常规治疗。因研究资料有限，未能进行漏斗图分析。"

References

[1] Murry CE, Wiseman RW, Schwartz SM,et al.Skeletal myoblast transplantation for repair of myocardial necrosis.J Clin Invest. 1996;98(11):2512-2523.
[2] Atkins D, Best D, Briss PA,et al.Grading quality of evidence and strength of recommendations.BMJ. 2004;328(7454): 1490.
[3] 尹作民,李长江,王燕,等.冠状动脉内注射自体骨髓干细胞改善急性心肌梗死患者的心功能[J].中国医药,2010,5(9):785-787.
[4] 李晓林,王志强,蒋锡初,等.冠状动脉内自体骨髓干细胞移植治疗急性心肌梗死[J].中国血液流变学杂志,2007,17(3):399-402.
[5] 李长江,尹作民,王燕,等.急性心肌梗死患者自体骨髓干细胞移植对改善心功能和VEGF影响的临床研究[J].中国临床新医学, 2010,3(4):302-305.
[6] 张清队,祁春梅,武维恒,等.经静脉和冠状动脉自体骨髓干细胞移植治疗急性心肌梗死的临床研究[J].实用医院临床杂志,2012, 9(3):61-64.
[7] 刘品发,佘海茹,高琴,等.西宁地区经冠状动脉自体骨髓干细胞移植治疗急性心肌梗死的临床研究[J].陕西医学杂志,2009,38(8): 965-967,1009.
[8] 晏凯利,陈苏,刘汉华.自体骨髓干细胞动员对急性心肌梗死患者心功能的影响[J].华中医学杂志,2008,32(5):335-337.
[9] 刘俊,游庆军,蒋锡初.自体骨髓干细胞移植对心肌梗死患者近期心功能的影响[J].山东医药,2006,46(30):13-14.
[10] 刘平,曾建平,黄河,等.自体骨髓干细胞移植治疗急性心肌梗死的临床研究[J].中国医师杂志,2006,8(10):1303-1305.
[11] 张宇燕,丁志坚,张馥敏,等.自体骨髓干细胞移植治疗心肌梗死患者心肌代谢及收缩功能的变化[J].江苏大学学报:医学版,2006, 16(5):416-420.
[12] Beitnes JO, Gjesdal O, Lunde K,et al. Left ventricular systolic and diastolic function improve after acute myocardial infarction treated with acute percutaneous coronary intervention, but are not influenced by intracoronary injection of autologous mononuclear bone marrow cells: a 3 year serial echocardiographic sub-study of the randomized-controlled ASTAMI study.Eur J Echocardiogr. 2011;12(2):98-106.
[13] Grajek S, Popiel M, Gil L,et al.Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial: Impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation.Eur Heart J. 2010; 31(6):691-702.
[14] Herbots L, D'hooge J, Eroglu E,et al.Improved regional function after autologous bone marrow-derived stem cell transfer in patients with acute myocardial infarction: a randomized, double-blind strain rate imaging study.Eur Heart J. 2009;30(6):662-670.
[15] Suárez de Lezo J, Herrera C, Pan M, et al.Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function.Rev Esp Cardiol. 2007;60(4):357-365.
[16] Schächinger V, Erbs S, Elsässer A, et al.Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006;355(12):1210-1221.
[17] Angoulvant D, Fazel S, Li RK.Neovascularization derived from cell transplantation in ischemic myocardium.Mol Cell Biochem. 2004;264(1-2):133-142.
[18] Uemura R, Xu M, Ahmad N,et al.Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling.Circ Res. 2006;98(11):1414-1421.
[19] Li ZQ, Zhang M, Jing YZ, et al.The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).Int J Cardiol. 2007;115(1):52-56.
[20] Martin-Rendon E, Brunskill SJ, Hyde CJ,et al.Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review.Eur Heart J. 2008;29(15):1807-1818.
[21] Zhao Q, Sun Y, Xia L,et al.Randomized study of mononuclear bone marrow cell transplantation in patients with coronary surgery.Ann Thorac Surg. 2008;86(6):1833-1840.
[22] Iwasaki H, Kawamoto A, Ishikawa M,et al.Dose-dependent contribution of CD34-positive cell transplantation to concurrent vasculogenesis and cardiomyogenesis for functional regenerative recovery after myocardial infarction. Circulation. 2006;113(10):1311-1325.
[23] Meluzín J, Janousek S, Mayer J,et al.Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction.Int J Cardiol. 2008;128(2):185-192.