Cell-Derived Therapies for Hypoplastic Left Heart Syndrome: A Meta-Analysis

Abstract

Background: Hypoplastic left heart syndrome is a severe single-ventricle congenital heart disease in which the right ventricle sustains systemic circulation after staged palliation. Cell-derived therapies have been investigated as adjunctive strategies to preserve ventricular function. This meta-analysis evaluated the safety and efficacy of cell-derived therapy in patients with hypoplastic left heart syndrome. Methods: PubMed, ScienceDirect, Wiley, and Cochrane were searched from inception to January 31, 2026. Database-specific search strings combined MeSH terms and free-text keywords for hypoplastic left heart syndrome, stem cells, cell-derived therapy, cardiosphere-derived cells, umbilical cord blood mononuclear cells, and mesenchymal precursor cells. Comparative human studies in HLHS or HLHS variants were included. Pooled odds ratios or mean differences with 95% confidence intervals were calculated using fixed-effect or random-effects models according to heterogeneity. Results: Six studies involving 218 patients were included. Cell-derived therapy improved right ventricular ejection fraction (mean difference, 4.61; 95% CI 0.28 to 8.94) and weight-for-age z score (MD 1.80; 95% CI 1.72 to 1.88). Mortality and hospital length of stay did not differ significantly between groups. Cardiopulmonary bypass time appeared shorter, but this finding was based on only two heterogeneous studies and should be interpreted cautiously. Conclusion: Adjunctive cell-derived therapy may improve ventricular function and somatic growth without a detectable early mortality signal, but the current evidence remains limited by small sample sizes, heterogeneity, and early-phase study designs.