Abstract
BACKGROUND: While heart failure with reduced ejection fraction (HFrEF) remains a major global health burden, mesenchymal stem cell (MSC) therapy has emerged as a promising intervention designed to improve cardiac function and reduce morbidity among patients unresponsive to conventional treatments. MSC therapy has shown promise by targeting left ventricular pressure and improving wall thickness, contributing to reductions in HF-related morbidity and mortality rates. This systematic review and meta-analysis bridges a gap in current research through a focused examination of the most recent clinical trials to cohesively assess MSC therapy in HFrEF patients. METHODS: We conducted a systematic review and meta-analysis of clinical trials published from 2018 onwards, which were obtained from multiple databases such as PUBMED, Scopus, EBSCO Medline, EBSCO CINAHL Science Direct, and the Cochrane Library. This review investigates the efficacy and safety outcomes of MSC therapy in patients above 18 years of age with a known diagnosis of heart failure with a reduced ejection fraction (HFrEF). The primary outcome was the change in the left ventricular ejection fraction (LVEF). Secondary outcomes encompassed several efficacy outcomes, such as Global Circumferential strain (GCS), the 6-Minute Walk Test (6MWT), Quality of Life (QoL), and major adverse cardiac events (MACE). A PRISMA flow diagram was constructed to illustrate the identification, screening, eligibility, and inclusion of studies at each stage of the review process. RESULTS: A total of 330 studies were initially identified, but only 12 met the inclusion criteria. MSC therapy resulted in a small, non-significant improvement in LVEF (Hedges' g = 0.096, p = 0.18) with low heterogeneity (I² = 0.5%). Only QoL showed significant improvement (Hedges' g = -0.518, p = 0.01). No significant changes in other efficacy outcomes were observed. The therapy was not associated with an increased risk of MACE. CONCLUSION: While MSC therapy was safe and improved QoL for HFrEF patients, it did not significantly improve LVEF or other efficacy outcomes. Further large-scale, standardized trials are required to better understand the potential role of MSCs in heart failure (HF) therapy.