Mononuclear Cell Therapy for Post-Fontan Cardiac Complications: A Comprehensive Systematic Review

Abstract

The Fontan procedure is a life-saving surgical intervention for children with single ventricle congenital heart disease, yet it often leads to long-term complications such as heart failure and liver disease. Emerging evidence suggests that intramyocardial injection of mononuclear cells (MNCs) may enhance cardiac performance and reduce myocardial fibrosis in this population. This review synthesizes clinical and experimental research on the application of MNC therapy in Fontan circulation, focusing on its effects on angiogenesis, inflammation, and cardiac function. Findings indicate that MNCs derived from bone marrow or umbilical cord blood can promote vascularization, reduce inflammatory responses, and improve ejection fraction and exercise tolerance. However, substantial variability in study designs, cell sources, and delivery methods limits the generalizability of current results. The therapeutic potential of MNC therapy is evident, but its translation into routine practice requires standardized protocols and large-scale, long-term clinical trials. MNC therapy represents a promising regenerative strategy for managing late complications following the Fontan procedure.