Efficacy and safety of stem cell therapy for myocardial infarction and heart failure: an updated systematic review and meta-analysis of randomized controlled trials

Abstract Background/objectives Cardiovascular diseases (CVDs), particularly myocardial infarction (MI) and heart failure (HF), remain global causes of morbidity and mortality, despite the current treatment options. Stem cell therapy (SCT) has emerged as a promising intervention aimed at halting disease progression and promoting cardiac repair. Nonetheless, the clinical efficacy, optimal cell type, delivery method, and safety profile of SCT remain inadequately defined. Methods This systematic review and meta-analysis aimed to evaluate the efficacy and safety of SCT in patients diagnosed with ischemic heart disease (IHD) and HF. PubMed, Web of Science, Embase, Scopus, and Science Direct were searched to retrieve randomized controlled trials (RCTs) investigating SCT in patients with MI or HF. Primary outcomes encompassed changes in left ventricular ejection fraction (LVEF), end-diastolic and end-systolic volumes (LVEDV, LVESV), infarct size, functional status, and quality of life measures. Risk ratios were calculated for safety outcomes. Subgroup analyses were executed based on follow-up duration, delivery method, and type of stem cell utilized. Results This review included 35 RCTs comprising 3345 patients (1875 in the SCT group and 1488 in the control group). The SCT indicated that significantly enhanced LVEF at 3, 6, and 12 months (mean difference [MD] = 1.43; 95% CI 0.92 to 1.95; p < 0.00001), while simultaneously reducing LVEDV (MD = − 5.23; 95% CI − 7.55 to − 2.91; p < 0.0001) and LVESV (MD = − 6.91; 95% CI − 9.01 to − 4.82; p < 0.00001). Additionally, infarct size demonstrated significant reductions at 6 and 12 months. Patients undergoing SCT exhibited improvements in functional status and quality of life. The safety profile of SCT indicated that it was well tolerated. Conclusions SCT appears to be a safe and modestly effective adjunctive therapy for patients with IHD and HF. The standardization of treatment protocols and the conduct of longer-term studies are critical to validate its clinical utility and optimize therapeutic outcomes. Systematic review registration: PROSPERO CRD42024582716