Abstract
INTRODUCTION: Stem cell therapy has emerged as a potential regenerative approach for Acute myocardial infarction (AMI). Despite decades of research and advancement in acute myocardial infarction (AMI) management, translating innovative therapies from bench to bedside remains a central challenge. Nonetheless, clinical outcomes exhibit considerable variability. This review provides a comprehensive overview of the clinical landscape of stem cell therapy for AMI, specifically focusing on how variations in cell type, delivery timing, routes, and dosages can affect cell therapy efficacy. METHODS: This study is a systematic review of randomized clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: After searching the relevant databases, a total of 5276 studies were assessed, and 43 trials were considered eligible for inclusion in the present systematic review. The safety and efficacy of various types of stem cells, including bone marrow-derived mononuclear cells (BM-MNCs), mesenchymal stem cells (MSCs), cardiac progenitor cells, and, more recently, induced pluripotent stem cells, have been evaluated in numerous clinical trials and meta-analyses. Among these, BM-MNCs and MSCs have been the most extensively studied. Although results vary from trial to trial and can even be contradictory, from frank failures to monumental achievements, overall, the evidence supports modest but statistically significant improvements in surrogate endpoints, such as left ventricular ejection fraction (LVEF), ventricular remodeling, and reduced infarct size. CONCLUSION: We have critically reviewed how methodological approaches-especially the definitions of endpoints and clinical outcome measures-have significantly influenced the reported efficacy and direction of the field. The interpretation of clinical trial results in cell therapy for AMI is heavily impacted by the specific metrics used to define success. A key focus is distinguishing between clinical trials on patients with acute and recent myocardial infarction (which is the main focus of this review) and those with chronic ischemic or non-ischemic cardiomyopathies, as they involve different treatment strategies. Patient selection is essential for improving responses in patients with AMI. Those with a severely reduced LVEF (LVEF < 40%) and younger age tend to benefit more. Limiting the transplantation window to the first 3-7 days after AMI may improve the intervention's effectiveness.