Combined umbilical cord-derived mesenchymal stem cell exosome and cell therapy in heart failure with reduced ejection fraction

Background Umbilical cord-derived mesenchymal stem cells (UC-MSCs) and their exosomes represent potential regenerative approaches for heart failure with reduced ejection fraction (HFrEF). This pilot study evaluated a combined UC-MSC-derived exosome and UC-MSC treatment strategy in HFrEF.Methods Ten male patients received intracoronary exosomes (20 × 109 particles) followed by two intravenous UC-MSC infusions (1 × 106 cells/kg) at one-week intervals. Echocardiographic parameters, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) scores were assessed longitudinally using linear mixed-effects models.Results LVEF increased at 3 months (β = 4.45%, p = 0.003), 6 months (β = 5.35%, p < 0.001), and 1 year (β = 4.66%, p = 0.002). Left ventricular dimensions decreased significantly at 6 months and 1 year. Log-transformed NT-proBNP decreased significantly only at 6 months (β = −0.54, p = 0.033), while KCCQ-12 scores did not change significantly. No treatment-related serious adverse events were identified; one patient developed transient pulmonary congestion.Conclusion The combined strategy was feasible and associated with modest improvements in cardiac function and ventricular dimensions. Given the small, uncontrolled pilot design, these findings are exploratory and do not establish efficacy or safety. Larger randomized controlled studies are required.