Updated Applications of Stem Cells in Hypoplastic Left Heart Syndrome

Hypoplastic Left Heart Syndrome (HLHS) is a severe congenital heart disease affecting 2-3 neonates every 10,000 live births. While prior research has highlighted potential genetic associations of HLHS, the precise pathophysiology remains elusive. Current standard of care involves three-staged surgical palliation that compensates for the underdeveloped left ventricle (LV) by redirecting systemic circulation via the right ventricle (RV). Despite surgical intervention, patients frequently experience complications of arrhythmias and right ventricular heart failure, culminating in the need for an eventual heart transplant. Scarcity of suitable donors combined with limited understanding of mechanisms of development highlights the need for further research into HLHS and alternative treatment options. Over the past decades, stem cell research has advanced our understanding of numerous cardiac conditions with significant implications for HLHS. This review outlines the emerging role of stem cell-based therapy with a focus on adult stem cells and pluripotent stem cells (PSC) in uncovering the pathophysiology of HLHS and optimizing future treatment directions. In addition, we will explore emerging directions of stem cell derived techniques such as cardiac organoids and bioengineering cardiac tissues and their utility for investigating disease mechanisms, drug screening, and novel therapy for HLHS.