Wang Zi, Wang Lingling, Su Xuan, Pu Jun, Jiang Meng, He Ben
Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
Stem Cell Res Ther. 2017 Jan 28;8(1):21. doi: 10.1186/s13287-016-0450-9.
Mesenchymal stromal cells (MSCs) are considered to have a modest benefit on left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI). However, the optimal injection timing and dose needed to induce beneficial cardiac effects are unknown. The purpose of this meta-analysis was to identify an optimal MSC transplantation time and cell dose in the setting of AMI to achieve better clinical endpoints.
The authors conducted a systematic review of studies published up to June 2016 by searching PubMed, EMBASE, MEDLINE, and the Cochrane Library for relevant randomized controlled trials (RCTs).
Eight prospective RCTs with 449 participants were included. The pooled results revealed that patients in the MSC group had no significant increase in LVEF from baseline compared with that in the control group (1.47% increase, 95% confidence interval (CI) -4.5 to 7.45; I = 97%; P > 0.05). A subgroup analysis was conducted to explore the results according to differences in transplantation time and dose of MSCs injected. For transplantation timing, the LVEF of patients accepting a MSC infusion within 1 week was significantly increased by 3.22% (95% CI 1.31 to 5.14; I = 0; P < 0.05), but this increase was insignificant in the group that accepted an MSC infusion after 1 week (-0.35% in LVEF, 95% CI -10.22 to 9.52; I = 99%; P > 0.05). Furthermore, patients accepting a MSC dose of less than 10 cells exhibited an LVEF improvement of 2.25% compared with the control (95% CI 0.56 to 3.93; I = 9%; P < 0.05). Combining transplantation time and cell dose indicates that a significant improvement of LVEF of 3.32% was achieved in the group of patients injected with <10 MSCs within 1 week (95% CI 1.14 to 5.50; I = 0; P = 0.003).
Transplantation time and injected cell dose are key factors that determine the therapeutic effect of stem cell therapy. The injection of no more than 10 MSCs within 1 week for AMI after percutaneous coronary intervention might improve left ventricular systolic function. Further studies on the mechanism and the effectiveness of MSCs for long-term therapy are warranted.
间充质基质细胞（MSCs）被认为对急性心肌梗死（AMI）患者的左心室射血分数（LVEF）有一定益处。然而，诱导有益心脏效应所需的最佳注射时间和剂量尚不清楚。本荟萃分析的目的是确定急性心肌梗死情况下MSCs移植的最佳时间和细胞剂量，以实现更好的临床终点。
作者通过检索PubMed、EMBASE、MEDLINE和Cochrane图书馆，对截至2016年6月发表的相关随机对照试验（RCT）进行了系统评价。
纳入了8项前瞻性RCT，共449名参与者。汇总结果显示，与对照组相比，MSCs组患者的LVEF从基线水平无显著增加（增加1.47%，95%置信区间（CI）-4.5至7.45；I² = 97%；P>0.05）。根据MSCs注射时间和剂量的差异进行亚组分析以探究结果。对于移植时间，在1周内接受MSCs输注的患者LVEF显著增加3.22%（95%CI 1.31至5.14；I² = 0；P<0.05），但在1周后接受MSCs输注的组中这种增加不显著（LVEF降低0.35%，95%CI -10.22至9.52；I² = 99%；P>0.05）。此外，接受MSCs剂量少于10⁶细胞的患者与对照组相比LVEF改善了2.25%（95%CI 0.56至3.93；I² = 9%；P<0.05）。综合移植时间和细胞剂量表明，在1周内注射少于10⁶个MSCs的患者组中LVEF显著改善了3.32%（95%CI 1.14至5.50；I² = 0；P = 0.003）。
移植时间和注射细胞剂量是决定干细胞治疗效果的关键因素。经皮冠状动脉介入治疗后1周内对AMI患者注射不超过10⁶个MSCs可能会改善左心室收缩功能。有必要对MSCs长期治疗的机制和有效性进行进一步研究。
