Adult Bone Marrow Cell Therapy for Ischemic Heart Disease: Evidence and Insights From Randomized Controlled Trials.
Adult Bone Marrow Cell Therapy for Ischemic Heart Disease: Evidence and Insights From Randomized Controlled Trials.
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DOI：
10.1161/circresaha.114.304792
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发表时间：
2015-08-28
影响因子：
20.1
通讯作者：
Dawn B
中科院分区：
文献类型：
--
作者：
Afzal MR;Samanta A;Shah ZI;Jeevanantham V;Abdel-Latif A;Zuba-Surma EK;Dawn B
尽管对于心脏修复的BMC疗法的结果存在不确定性，但迫切需要进一步的见解来改进这一有希望的方法。通过对符合条件的随机对照试验(RCT)的数据进行系统回顾和荟萃分析，描述BMC疗法对心脏修复的真正影响，并为未来的试验提供见解。截至2014年8月的数据库搜索确定了48名符合条件的随机对照试验(登记了2602名患者)。采用随机效应Meta分析方法对左心室射血分数(EF)、心肌梗死面积、左心室收缩末期容积(LVESV)、左心室舒张末容积(LVEDV)的变化进行加权平均分析。与标准治疗相比，骨髓细胞移植可改善左心室射血分数(2.92%；95%可信区间，1.91至3.92；P<；0.00001)，缩小心肌梗死面积(−2.25%；95%CI，−3.55至−0.95；P=0.0007)和左心室收缩末容积(−6.37ml；95%CI，−8.95至−3.80；P<；0.00001)，并有降低左心室射血分数(−2.26ml；95%CI，−4.59至0.07；P=0.06)。在排除了结果报告中存在差异的研究后对数据进行分析时，也注意到了类似的影响。当对照组患者也进行心导管术时，这种益处也持续存在。尽管成像方式对结果有一定影响，但在MRI评估时，接受骨髓基质细胞治疗的患者的LVEF有所改善。心肌梗死后早期(48小时)注射BMC对缩小心肌梗死面积更有效，而3~10天注射BMC对改善心脏收缩功能更有效。至少5000万个骨髓细胞似乎是必要的，随着细胞数量的增加，额外的好处有限。BMC治疗是安全的，并改善了临床结果，包括全因死亡率、复发的MI、室性心律失常和随访期间的脑血管意外(CVA)，尽管急性MI和慢性IHD亚组之间存在差异。成人骨髓细胞移植改善了IHD患者的LVEF，缩小了梗塞面积，改善了重构。这些影响在使用MRI的研究分析中得到支持，在排除了结果报告不一致的研究后也得到了支持。骨髓间充质干细胞移植还可以减少随访期间死亡、再发心肌梗死、室性心律失常和CVA的发生率。
Notwithstanding the uncertainties regarding the outcomes of BMC therapy for heart repair, further insights are critically needed to improve this promising approach. To delineate the true impact of BMC therapy for cardiac repair and gain insights for future trials through systematic review and meta-analysis of data from eligible randomized controlled trials (RCTs). Database searches through August 2014 identified forty-eight eligible RCTs (enrolling 2602 patients). Weighted mean differences for changes in left ventricular (LV) ejection fraction (EF), infarct size, LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were analyzed with random-effects meta-analysis. Compared with standard therapy, BMC transplantation improved LVEF (2.92%; 95% confidence interval [CI], 1.91 to 3.92; P<0.00001), reduced infarct size (−2.25%; 95% CI, −3.55 to −0.95; P=0.0007) and LVESV (−6.37 ml; 95% CI, −8.95 to −3.80; P<0.00001), and tended to reduce LVEDV (−2.26 ml; 95% CI, −4.59 to 0.07; P=0.06). Similar effects were noted when data were analyzed after excluding studies with discrepancies in outcomes reporting. The benefits also persisted when cardiac catheterization was performed in control patients as well. Although imaging modalities partly influenced the outcomes, LVEF improved in BMC-treated patients when assessed by MRI. Early (<48h) BMC injection after MI was more effective in reducing infarct size, while BMC injection between 3 and 10 days proved superior toward improving systolic function. A minimum of 50 million BMCs seemed to be necessary, with limited additional benefits seen with increasing cell numbers. BMC therapy was safe and improved clinical outcomes, including all-cause mortality, recurrent MI, ventricular arrhythmia, and cerebrovascular accident (CVA) during follow-up, albeit with differences between acute MI and chronic IHD subgroups. Transplantation of adult BMCs improves LVEF, reduces infarct size and ameliorates remodeling in patients with IHD. These effects are upheld in analyses of studies employing MRI, and also after excluding studies with discrepant outcomes reporting. BMC transplantation may also reduce the incidence of death, recurrent MI, ventricular arrhythmia, and CVA during follow-up.