Abstract 3230: Cardiac Stromal-derived Cells Reveal Higher Proficiency to Myocardial Regeneration Than Bone Marrow Mesenchymal Cells With Identical Genetic Background
INTRODUCTION: Object of this study was to investigate whether mesenchymal-like stromal cells of cardiac origin (CSC) contribute to cardiac regeneration and functional improvement in comparison to bone marrow (BM) stromal cells (BMSC). Specifically, we compared the in vitro and in vivo properties of a series of CSC and BMSC derived from the same patients to avoid confounding differences linked to genetic background.
METHODS & RESULTS: CSC and BMSC populations showed low immunogenic properties, presented similar surface markers and expressed comparable levels of Nanog, MDR-1, Oct4 and KLF4; (n=8). Further characterizations, however, revealed remarkable differences summarized as the following:
CSC expressed from 30 to 2500 fold higher levels of the transcription factors GATA6 and GATA4, respectively;
BMSC, but not CSC, stained positive to the Von Kossa reagent and acquired alkaline phosphatase activity when cultured in an osteogenic medium, (n=4);
BMSC, cultured in adipogenic medium, revealed a higher increase in PPAR-γ2 (550 fold vs 12), Adipsin (150 fold vs 7) and Oil-Red-O content than CSC, (n=3);
when cultured in an endothelial-specific medium, CSC, more than BMSC, acquired the expression endothelial-specific markers, including CD144 (32.90%±12.89 CSC vs 0.67%±0.30 BMSC), VEGFR2 (30.52%±12.52 CSC vs 2.94%±2.12 BMSC), and CD31 (22.99%±7.80 CSC vs 0.93%±0.90 BMSC, n=6) and efficiently formed capillary-like structures on a cultrex layer, (n=4).
CSC, treated with All-Trans Retinoic Acid and Phenyl-butyrate, exhibited a gene expression pattern more oriented towards the cardiomyogenic lineage than that of BMSC, as demonstrated by a significant increase in α-MHC (6 fold), Troponin-I (7 fold) and α-sarcomeric actin (8 folds; n=12).
In vivo, injected in rats with chronic myocardial infarction, CSC persisted within the ischemic tissue, migrated into the scar, differentiated into cardiomyocytes and improved cardiac function more efficiently than their BM counterpart; (n=7).
CONCLUSIONS: Although CSC and BMSC share a common phenotype, CSC are more sensitive to vasculogenic and cardiogenic signals and may represent a cellular source suitable for more efficient cardiac repair.