Abstract 16066: Isolation and Functionality of Cardiac Progenitor Cells in Congenital Heart Patients
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 warrants exploration, especially for CHD patients with congestive heart failure. We aimed to define the optimal cardiac chamber source for isolating the hCPCs and to determine how the number of isolated hCPCs changes with CHD patient characteristics, such as age, diagnosis, and cyanosis.
Methods and Results: Human specimens (120 samples) were obtained during routine congenital cardiac surgical procedures from three age groups: neonates (<30 days), infants (1 month -2 years), and children (> 2 years - ≤13 years). Using c-kit expression as a specific marker for hCPCs, we showed that the hCPCs was three-fold higher in neonates versus children > 2 years (8.9%±0.4% vs 3.2%±0.1%, p<0.01) in tissue sections. We developed a reproducible isolation method for the hCPCs (120 samples from 120 patients) that grew in culture with stem cell expansion media. Analysis by immunofluorescence demonstrated that cultured hCPCs derived from the right atrium (5.2%±1.2%) generated higher amounts of hCPCs in culture than did cultured cells from the left atrium (0.3%±1.1%), right ventricle (1.4%±0.7%) and left ventricle (1.4%±0.6%, p<0.05). These hCPCs were isolated regardless of patient's age or diagnosis, including cyanotic CHD. The hCPCs were multipotent and differentiated into diverse cardiovascular lineages in vitro. Finally, we demonstrated their functionality by transplanting the hCPCs into infarcted myocardium of rats where the hCPCs generated myocardial grafts and improved the ejection fraction when compared to controls (43%±1.3% vs.30%±1.5%, p<0.01%).
Conclusions: This is the largest characterization of resident hCPCs within young human myocardium. We demonstrate that the right atrium is the best source for functional hCPCs and that these cells may be potentially used in regenerative strategies for CHD patients with congestive heart failure.
- © 2010 by American Heart Association, Inc.