Abstract 131: Age dependent regenrative ability of ckit+ cells Derived from Neonatal and adult Hearts

Abstract

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 neonatal-derived ckit + CSCs 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. More than 85% ckit+ cells were isolated from both groups and these cells were negative for tryptase, collagen, CD45, CD34 and CD31. Single cell proliferation assay showed neonatal ckit+ cells are significantly more proliferative compare to adult ckit + cells. Neonatal c-kit + cells showed significantly higher telomere length (p=0.0286) compare to Adult. 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. . Treatment with Neonatal-derived ckit + cells also augmented the preservation/formation of neovessels (isolectin B4) and arterioles (α-SMA) compared to adult-derived ckit + cells Conclusions: 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.