Intracoronary Autologous Bone Marrow-Derived Cell Therapy in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objectives: Intracoronary autologous bone marrow-derived cell therapy has been proposed to enhance myocardial repair after Acute Myocardial Infarction (AMI), but the included cell products and trial designs vary considerably across the RCT literature. Methods: PubMed, Embase, Cochrane CENTRAL, Scopus and Web of Science were searched from inception to 2025 for randomized controlled trials of intracoronary autologous bone marrow-derived cell therapy (Bone Marrow Mononuclear Cells [BMMNC], BMMNC/peripheral blood mononuclear cell mixtures, or selected CD34+/BMMNC combinations) versus standard care following AMI, reporting change in Left Ventricular Ejection Fraction (LVEF). Study selection, data extraction and Risk-of-Bias assessment (Cochrane RoB 2.0) were performed by a single reviewer. Random-effects meta-analysis (DerSimonian-Laird, with a Paule-Mandel estimator as a sensitivity analysis) was used to pool the Mean Difference (MD) in LVEF. This review was not prospectively registered. Results: Six RCTs (738 patients: 411 cell therapy, 327 control) met inclusion criteria. Pooled LVEF change favored cell therapy (MD +1.60%; 95% CI 0.72-2.47; I² = 0%), a result unchanged under the Paule-Mandel sensitivity estimator. No significant effects were observed for all-cause mortality (RR 0.94; 95% CI 0.71-1.25), major adverse cardiac events (MACE; RR 0.89; 95% CI 0.68-1.16), or infarct size (MD-1.5%; 95% CI-3.8 to 0.8). Certainty of evidence, graded by GRADE, ranged from low to very low across outcomes, driven primarily by risk of bias and imprecision. Conclusion: Intracoronary autologous bone marrow-derived cell therapy produces a small, statistically significant improvement in LVEF after AMI, without a demonstrated effect on mortality, MACE, or infarct size in this dataset. The clinical relevance of the LVEF effect remains uncertain and the certainty of the underlying evidence is low.