Cardiac Stem Cell Treatment in Myocardial Infarction: A Systematic Review and Meta-Analysis of Preclinical Studies

Abstract

RATIONALE: Cardiac stem cells (CSC) therapy has been clinically introduced for cardiac repair after myocardial infarction (MI). To date there has been no systematic overview and meta-analysis of studies using CSC therapy for MI. OBJECTIVE: Here, we used meta-analysis to establish the overall effect of CSCs in preclinical studies and assessed translational differences between and within large and small animals in the CSC therapy field. In addition, we explored the effect of CSC type and other clinically relevant parameters on functional outcome to better predict and design future (pre)clinical studies using CSCs for MI. METHODS AND RESULTS: A systematic search was performed, yielding 80 studies. We determined the overall effect of CSC therapy on left ventricular ejection fraction (EF) and performed meta-regression to investigate clinically relevant parameters. We also assessed the quality of included studies and possible bias. The overall effect observed in CSCs treated animals was 10.7% (95%CI 9.4-12.1 p<0.001) improvement in EF compared to placebo controls. Interestingly, CSC therapy had a greater effect in small animals compared to large animals (p<0.001). Meta-regression indicated that cell type was a significant predictor for EF improvement in small animals. Minor publication bias was observed in small animal studies. CONCLUSIONS: CSC treatment resulted in significant improvement of EF in preclinical animal models of MI compared to placebo. There was a reduction in the magnitude of effect in large compared to small animal models. Although different CSC types have overlapping culture characteristics, we observed a significant difference in their effect in post-MI animal studies.