Abstract 13138: A Strong Regenerative Ability of Cardiac Progenitor Cells in Hypoplastic Left Heart Syndrome Patients: A Preclinical Study
Background: Human cardiac progenitor cells (hCPCs) may promote myocardial regeneration in adult ischemic myocardium. The regenerative capabilities of hCPCs in young patients with non-ischemic congenital heart defects (CHD) for potential use in congenital cardiac repair strategies has not been explored, especially in hypoplastic left heart syndrome (HLHS) patients. We hypothesized that isolated HLHS patient - derived hCPCs have a higher regenerative ability than hCPCs derived from other CHD patients and adult ischemic patients.
Methods and Results: Human specimens (20 samples) were obtained during routine cardiac surgical procedures from discarded right atrial appendage tissue from 3 age groups: neonatal HLHS patients, children (> 2 years-<13years), and adults (>45years). Using c-kit expression as a specific marker for hCPCs, we showed with immunohistochemistry that the number of hCPCs were highest in neonatal HLHS patients and decreased with advancing age as the adult patients had the lowest number (8.3%±1.2% vs. 0.5%±1.3%, P<0.01). We developed a reproducible isolation method for the hCPCs (20 samples from 20 patients) that grew in culture with stem cell expansion media. The hCPCs were multipotent and differentiated into diverse cardiovascular lineages in vitro. Finally, we demonstrated their functional regenerative ability by transplanting the hCPCs into infarcted myocardium of nude rats. The HLHS patient-derived hCPCs had the highest ability to generate myocardial grafts and improved the ejection fraction when compared to adult-derived hCPCs(43%±1.3% vs.35%±1.5%, p<0.01) and to controls (43%±1.3% vs.30%±1.5%, p<0.001).
Conclusions: The HLHS patient-derived hCPCs are easily isolated, expanded, and have strong regenerative ability which has important implications for using them in clinical protocols for HLHS patients.
- Hypoplastic left heart
- Stem/progenitor cells
- Congenital heart surgery
- Regenerative medicine stem cells
- Heart failure
- © 2011 by American Heart Association, Inc.