Abstract 11237: Human Epicardial Fat is a Superior Source for Mesenchymal Stromal Cells with Reparative and Regenerative Properties
BACKGROUND: One of the major challenges in cardiovascular regenerative medicine is to determine the optimal cell source for heart repair. We aimed to test the hypothesis that adipose tissue surrounding the heart is a better cell source of mesenchymal stromal cells (MSCs) for cardiovascular regeneration and repair, compared with peripheral adipose tissue and resident cardiac progenitors.
METHODS and RESULTS: We isolated and grew cells from tissue samples from the right atrium and 4 different sources of adipose tissue: epicardial, pericardial, thymus, and abdominal liposuction. All cultured cells displayed a mesenchymal spindle shape, expressed high levels of human MSC markers: CD105, CD73, CD90, and lacked the hematopoietic lineage markers CD45 and CD34. However, only atrial MSCs expressed c-Kit (41.7%). MSCs differentiated into osteogenic and adipogenic lineages after incubation with special culture medium. MSCs derived from the right atrium, epicardial and pericardial adipose tissue expressed cardiomyocyte contractile protein such as cardiac troponin-I and α-actinin after incubation with de-methylating agent 5-azacytidine. We next evaluated the cells' cytokine secretion profiles, and found reparative properties in the atrial- and epicardial-derived MSCs. Interestingly, these cells secreted the highest levels of trophic factors such as bFGF and HGF (p<0.05). To examine the cells' differentiation capacity in vivo, epicardial adipose tissue-derived cells were injected into immune-compromised nude rat myocardium. Immunostaining for human actin and actinin revealed early sarcomere formation in the implanted human cells one week after the injection. Finally, epicardial adipose tissue-derived cells were injected into ischemic hind limb of mice (Balb/C, n=10) and improved perfusion, compared with control, 10 days after injection (304.9% vs. 57.5% p<0.0001).
CONCLUSIONS: Human epicardial fat provides a viable and rich source of MSCs with unique reparative properties that might save the need for myocardial biopsy. Compared with pericardial and peripheral fat, these cells have many similarities to atrial-derived cardiac progenitors and have improved regenerative potential.
- © 2011 by American Heart Association, Inc.