Cardiac stem cell therapies for congenital heart diseases

During the last 2 decades, stem cell therapies with bone marrow mononuclear cells (BMMNCs) or mesenchymal stem cells (MSCs) to treat ischemic heart disease, including in pre-clinical and clinical trials, have demonstrated the ability of stem cells to improve cardiac function, infarct size, and cardiac remodeling in adult patients. In recent years, endogenous cardiac stem cells (CSCs) derived from heart tissue have been identified. CSCs have been shown to have superior regenerative potential over other types of stem cells in terms of cardiovascular-lineage differentiation, paracrine factor secretion, and functional improvement after cell transplantation. Cardiac stem cell therapy to regenerate damaged myocardium after chronic infarction has been reported in the SCIPIO and CADUCEUS trials. In contrast, although recent advances in pediatric cardiology, congenital cardiac surgery, and intensive care management have dramatically changed clinical outcomes, there is an increasing recognition of limited therapeutic improvement in children with severe heart failure. Congenital heart failure is a structural heart disease caused by multiple etiologies related to pressure and volume overload, arrhythmia, and myocardial degradation. Stem cell-based strategies to treat heart failure in adults have been investigated; however, little is known about their safety and efficacy in children and planned clinical studies are quite limited. Only case reports have been published and no large clinical trials have been conducted using any type of stem cells. Recently, the TICAP trial has revealed the safety and feasibility of intracoronary infusion of autologous cardiosphere-derived cells (CDCs) in children with hypoplastic left heart syndrome (HLHS). Although this trial had several limitations that required further evaluation, the results from this study provided a foothold for stem cell-based therapeutic strategies in patients with congenital heart disease. Eventually, a new paradigm of stem cell therapy to treat congenital heart failure has started to form. Many important issues including long-term cell engraftment, the mechanism of stem cell recruitment and differentiation, administration route, and appropriate cell types to deliver in situ remain to be investigated. Here, we review the latest research on stem cell therapies for heart failure and discuss the future perspectives on cell-based regenerative strategies to treat patients with congenital heart diseases.