Mesenchymal Stem Cell Transplantation in Patients With Acute Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

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 answered, such as the best seed cells, transplant dosage, and transplant timing. We conducted a meta-analysis of randomized controlled trials to explore the issues related to the treatment of AMI based on mesenchymal stem cells (MSCs) transplantation and to guide the design of subsequent clinical studies to achieve better clinical endpoints.Methods: The Pubmed, Embase databases, and Cochrane Library were searched for clinical studies between January 1, 2000, and January 23, 2021. Studies that evaluated the effect of MSCs transplantation on AMI were identifified. According to the Cochrane systematic review method, the literature quality of the included studies was evaluated, and valid data were extracted. RevMan 5.3 and Stata 15.1 software were used for Meta-analysis.Results: After a literature search and detailed evaluation, 9 randomized controlled trials with a total of 460 individuals were included in the quantitative analysis. Pooled analyses indicated that MSCs transplantation was associated with a greater improvement of left-ventricular ejection fraction (LVEF) (mean difference [MD], 3.08%; 95% confidence interval [CI], 1.81 to 4.35; P< 0.00001; I2=89%) than controls. A subgroup analysis was conducted to explore the results according to differences in follow-up time, transplantation dose and time of MSCs injected. The improvement effect of LVEF was maintained for up to 24 months after MSCs treatment. For transplantation dose, the LVEF of patients who accepted a MSC dose of 107-108 cells exhibited an LVEF improvement of 2.62% (95% CI 1.54 to 3.70; P < 0.00001; I2 =0%), but this improvement was insignificant in the subgroup that accepted a MSC 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 control. The LVEF of patients accepting a MSCs infusion within 2 to 14 days after Percutaneous coronary intervention (PCI) was significantly increased by 3.18% (95% CI, 2.89 to 3.47; P<0.00001; I2 = 0). MSCs therapy was not associated with an increased risk of major adverse events.Conclusion: Results from our systematic review suggest that MSCs transplantation can improve the heart function of patients with AMI, and the effect was maintained for up to 24 months. MSC 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 may be within 2-14 days after PCI.

Mesenchymal Stem Cell Therapy for a Better Prognosis of Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…A few existing meta-analyses have also investigated the association between MSCs and manifestations of ischemic heart disease, such as acute myocardial infarction [ 27 , 29 - 31 ]. It is important to note that ischemic heart disease is a prominent causative agent of HF, and thus it is crucial to review the results of these analyses [ 32 ].…”