Abstract 243: End Stage heart Failure Cardiac Stem Cells has Strong Regenerative Ability compared to Congenital Heart Cardiac Stem cells
Cellular based therapy is an important component of cardiac regenerative medicine. We have already identified and characterized a small population of undifferentiated cells present throughout the human heart that have the characteristics of cardiac stem cells. To date, no study has examined the potential application of human cardiac derived stem cells (hCDCs) generated from End Stage Heart Failure (ESFH) pediatric patient’s heart. In this study, we characterized samples from ESFH (recipients of heart transplant) and CDH (donors of the heart transplantation) to quantify the expression of various cardiac progenitor markers by immunofluorescence, flow cytometry and RT-PCR. The numbers of cardiac progenitor cells were highest in the right atria as compared to other chambers of the end-stage heart. FACS and IF analysis demonstrated significantly higher c-kit (9.36±1.384 vs 3.056±0.39, n=5) and ISL1 (33.61±4.0 vs 3.708±0.93) expressions in hCDCs derived from ESFH compare to CDH myocardium. Also, there was a tendency for increased FLK1 and Sca-1 expression in ESFH patients respectively. To determine, the functional potential, hCDCs were transplanted into a rodent myocardial infarct (MI) model. ESFH-derived hCDCs produced a stronger recovery of ventricular function than CDH-derived hCDCs (ESFH, n=5, EF=57+3% vs. CDH, n=5, 41.5±3%, P<0.05). We also observed significantly higher secretion of VEGF (ESFH, n=5: 1.928±0.3623 vs CDH, n=5: 0.93±0.08, P<0.05) and SDF-1α (ESFH, n=5: 3.1±0.6934 vs CDH, n=5: 0.99±0.1471, P<0.05) by the ESFH-derived hCDCs as compared to CDH-derived hCDCs. This correlated with increased angiogenesis in the MI model at 28days. This study demonstrates that ESFH-derived hCDCs are highly functional and secrete angiogenic cytokines, more than CDH-derived hCDCs. To understand the mechanism of this activity will be critical for future clinical study.
- © 2013 by American Heart Association, Inc.