Efficacy and Safety of Mesenchymal Stem Cell Therapy in Patients with Acute Myocardial Infarction: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background and Objectives: The adjuvant treatment of stem cell therapy for acute myocardial infarction (AMI) has been studied in multiple clinical trials, but many questions remain to be addressed, such as efficacy, safety, identification of the optimal cell type, tractable route of delivery, transplant dosage, and transplant timing. The current meta-analysis aimed to explore the issues of mesenchymal stem cells (MSCs) transplantation in patients with AMI based on published randomized controlled trials (RCTs) and guide the design of subsequent clinical trials of MSCs therapy for AMI. Methods: The Cochrane Library, PubMed, EMBASE databases were searched for relevant clinical trials from January 1, 2000, to January 23, 2021. Results from RCTs involving MSCs transplantation for the treatment of AMI were identified. According to the Cochrane systematic review method, the literature quality, including studies, was evaluated and valid data was extracted. Rev- Man 5.3 and Stata 15.1 software were used for Meta-analysis. Results: After literature search and detailed evaluation, 9 randomized controlled trials enrolling 460 patients were included in the quantitative analysis. Pooled analyses indicated that MSCs therapy was associated with a significantly greater improvement in overall left ventricular ejection fraction (LVEF), and the effect was maintained for up to 24 months. No significant difference in favor of MSCs treatment in left ventricular (LV) volume and in the risk of rehospitalization as a result of heart failure (HF) was noted, compared with the controls. For transplantation dose, the LVEF of patients accepting a MSCs dose of 107-108 cells was significantly increased by 2.62% (95% CI 1.54 to 3.70; P < 0.00001; I2 =0%), but this increase was insignificant in the subgroup that accepted a MSCs dose of < 107 cells (1.65% in LVEF, 95% CI, 0.03 to 3.27; P =0.05; I2 =75%) or >108 cells (4.65% in LVEF, 95% CI, -4.55 to 13.48; P =0.32; I2 =95%), compared with the controls. For transplantation timing, a significant improvement of LVEF of 3.18% was achieved in the group of patients accepting a MSCs infusion within 2 to 14 days after percutaneous coronary intervention (PCI) (95% CI, 2.89 to 3.47; P <0.00001; I2 = 0). There was no association between MSCs therapy and major adverse events. Conclusion: Results from our systematic review suggest that MSCs therapy for patients with AMI appears to be safe and might induce a significant increase in LVEF with a limited impact on LV volume and rehospitalization caused by HF. The effect was maintained for up to 24 months. MSCs dose of 107-108 cells was more likely to achieve better clinical endpoints than <107 or >108 cells. The optimal time window for cell transplantation might be within 2-14 days after PCI. This meta-analysis was registered with PROSPERO, number CRD 42021241104.