Abstract 18377: Hypoplastic Left Heart Syndrome Derived Cardiac Stem Cells Show a Strong Regenerative Ability
Background: Human adult c-kit+ cardiac stem cells (CSCs) alleviates post-myocardial infarction left ventricle dysfunction in animal models and a Phase I clinical study. The regenerative capacity of CSCs in the very young patients with non-ischemic congenital heart defects has not been explored, even in the most surgically challenging Hypoplastic Left Heart Syndrome (HLHS) patients. We hypothesized that isolated HLHS neonatal-derived CSCs may have higher regenerative abilities than adult-derived CSCs and might address the anatomical deficiency of HLHS myocardium.
Methods and Results: Human specimens were obtained during routine cardiac surgical procedures from right atrial appendage tissue discarded from 2 age groups: neonates and adults patients. We developed a reproducible isolation method that generated c-kit+ cells using immune-activated magnetic bead selection, regardless of the initial weight or age. Both groups had similar expression profile for c-kit+ (>85%), Ki67, TnT, GATA4+, and were negative for tryptase, collagen, and CD45. Both groups had similar proliferation doubling times. The neonatal-derived c-kit+ cells secreted higher levels of VEGF-A, ANG, and SDF-1α when compared to adult-derived c-kit+ cells. When transplanted into infarcted myocardium, neonatal-derived c-kit+ cells had a significantly higher ability to preserve myocardial function, prevent adverse remodeling, and enhance blood vessel preservation when compared to adult-derived c-kit+ CSCs.
Conclusions: HLHS neonatal-derived c-kit+ cells have a strong regenerative ability when compared with adult-derived c-kit+ cells that may depend on angiogenic cytokines. This has important implications in the potential use of CSCs in future HLHS clinical trials.
- Myocardial infarction
- Stem cell therapy
- Pediatric cardiology
- Adult congenital heart disease
- Cardiac regeneration
- © 2013 by American Heart Association, Inc.