Abstract 9276: Optimizing Cardiac Progenitor Cell-Sheet Therapy by Adding Endothelial Progenitor Cell Transplantation for Ischemic Cardiomyopathy: An Analysis of Layer-Specific Regional Cardiac Function
Background: Transplantation of cell-sheet generated by cardiac progenitor cells (CPCs) is a promising therapeutic strategy for ischemic cardiomyopathy (ICM), while potential ischemia in the transplanted area remains to be overcome. Endothelial progenitor cells (EPCs) reportedly induce angiogenesis in the injected territory.
Hypothesis: Concomitant EPC injection might enhance the therapeutic effects of CPC cell-sheet in ICM.
Methods: Scaffold-free CPC cell-sheet was generated from human primary c-kit+ heart-derived cells. ICM model was generated by placing the ameroid ring around the left coronary artery for 4 weeks in swine. They then underwent sham operation, CPC cell-sheet transplantation over the epicardial infarct area, or cell-sheet plus human EPC i.m. injection (n=5 in each), followed by the efficacy assessment for 2 months.
Results: Speckle-tracking echocardiography dissected layer-specific regional systolic function by the radial strain. The epicardial radial strain in the infarct area was similarly greater after the CPC sole (19±5%) and the combination (20±5%) than that after the sham (7±1%, P=0.01). In contrast, the endocardial radial strain in the infarct area was greater after the combination (14±2%) than that after the CPC sole (11±2%, P=0.04) or the sham (9±1%, P=0.02), suggesting addition of EPC injection may enhance the functional recovery in the endocardium. Consequently, significant improvement in the left ventricular ejection fraction by the CPC sole therapy (43±5%, P=0.03) compared to the sham (32±4%) was further enhanced by the combination therapy (53±4%, P=0.01), assessed by the multi-detector-raw CT. Consistently, histological findings, including in-situ hybridization with human specific primers, revealed additional EPC injection significantly increased capillaries in the infarct area (272±38/mm2 vs. 195±32/mm2 vs. 85±26/mm2) and induced differentiation of transplanted CPCs into the myogenic and endothelial lineages.
Conclusion: Transplantation of CPC cell-sheet induced functional recovery in the epicardial infarct area, whereas concomitant EPC transplantation achieved a transmural recovery associated with enhanced neovascularization and possible cardiomyogenic differentiation in ICM.
- Endothelial progenitor cell
- Experimental heart failure
- Ischemic heart disease
- Stem/progenitor cells
- Stem cell therapy
- © 2011 by American Heart Association, Inc.