Stem cell transplantation dose in patients with acute myocardial infarction: A meta-analysis

OBJECTIVE To evaluate whether stem cell transplantation improves global left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI), and to determine the appropriate stem cell therapy dose as well as the effective period after stem cell transplantation for therapy. METHODS A systematic literature search included Pubmed, MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Cochrane Evidence-Based Medicine databases. The retrieval time limit ranged from January 1990 to June 2016. We also obtained full texts through manual retrieval, interlibrary loan and document delivery service, or by contacting the authors directly. According to our inclusion and exclusion criteria, data were extracted independently by two evaluators. In case of disagreement, a joint discussion occurred and a third researcher was utilized. Data were analyzed quantitatively using Revman 5.2. Summary results are presented as the weighted mean difference (WMD) with 95% confidence intervals (CIs). We collected individual trial data and conducted a meta-analysis to compare changes in global left ventricular ejection fraction (ΔLVEF) after stem cell therapy. In this study, four subgroups were based on stem cell dose (≤1 × 107 cells, ≤1 × 108 cells, ≤1 × 109 cells, and ≤1 × 1010 cells) and three subgroups were based on follow-up time (<6 months, 6-12 months, and ≥12 months). RESULTS Thirty-four studies, which included 40 randomized controlled trials, were included in this meta-analysis, and 1927 patients were evaluated. Changes in global LVEF were significantly higher in the stem cell transplantation group than in the control group (95% CI: 2.35-4.26%, P < 0.01). We found no significant differences in ΔLVEF between the bone marrow stem cells (BMCs) group and control group when the dose of BMCs was ≤1 × 107 [ΔLVEF 95% CI: 0.12-3.96%, P = 0.04]. The ΔLVEF in the BMCs groups was significantly higher than in the control groups when the dose of BMCs was ≤1 × 108 [ΔLVEF 95% CI: 0.95-4.25%, P = 0.002] and ≤1 × 109 [ΔLVEF 95% CI: 2.31-4.20%, P < 0.01]. In addition, when the dose of BMCs was between 109 and 1010 cells, we did not observe any significant differences [ΔLVEF 95% CI: -0.99-11.82%, P = 0.10]. Our data suggest stem cell therapy improves cardiac function in AMI patients when treated with an appropriate dose of BMCs. CONCLUSION Stem cell transplantation after AMI could improve global LVEF. Stem cells may be effectively administered to patients with AMI doses between 108 and 109 cells.