Rational transplant timing and dose of mesenchymal stromal cells in patients with acute myocardial infarction: a meta-analysis of randomized controlled trials

BACKGROUND: 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. METHODS: 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). RESULTS: 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 (2) = 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 (2) = 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 (2) = 99%; P > 0.05). Furthermore, patients accepting a MSC dose of less than 10(7) cells exhibited an LVEF improvement of 2.25% compared with the control (95% CI 0.56 to 3.93; I (2) = 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(7) MSCs within 1 week (95% CI 1.14 to 5.50; I (2) = 0; P = 0.003). CONCLUSIONS: 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(7) 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.