Abstract 8791: Intracoronary Allogenic Mesenchymal Stem Cells (icMSCs) and Oral Pravastatin Increase cKit+/CD45- Progenitor Cells and Synergistically Enhance Cardiomyocyte Differentiation in Swine with Chronic Ischemic Cardiomyopathy
Background: icMSCs amplify the myocyte proliferation occurring after the HMG-CoA reductase inhibitor pravastatin in viable chronically dysfunctional myocardium devoid of infarction. We tested the hypothesis that this synergistic effect is related to increasing cKit+/CD45- progenitor cell numbers and/or their myocyte lineage commitment.
Methods: Swine with ischemic cardiomyopathy from chronic LAD and LC stenoses with resting dysfunction (n=6) were compared to similar animals treated for 4-weeks with pravastatin (80mg/day, Prava, n=8) or both pravastatin and 20x106 allogenic icMSCs (Prava+MSCs, n=8). MSC uptake was assessed with Y-FISH in sex mismatched recipients (n=4). We quantified total cKit+/CD45− progenitor cells in the myocardium. Progenitor cells differentiating into a myocyte lineage were quantified by colocalization with GATA4 or cardiac troponin I (cTnI).
Results: Prava+MSCs increased myocyte nuclear density more than Prava alone (Table) and led to a greater increase in ejection fraction. Y-FISH staining demonstrated that 3.2 ± 1.3 % of injected MSCs (2.7 ± 0.9 MSCs/100mm2) were retained in the LV and predominantly localized in the interstitial space. This was an order of magnitude lower than myocardial cKit+/CD45- cells. No Y-FISH positive cardiac cells were identified. While both treatments increased cKit+/CD45- cells vs. untreated animals, the combination of icMSCs with Prava enhanced the number of cells with a myocyte lineage commitment as reflected by increased colocalization with GATA4 and cTnI (Table).
Conclusion: While icMSCs added to background treatment with Prava do not increase the number of cKit+/CD45- cells, they enhance differentiation into a cardiac lineage resulting in a significantly higher myocyte nuclear density. The failure to identify Y-FISH positive cardiac myocytes provides further support for the paracrine nature of the actions of icMSCs.
- © 2010 by American Heart Association, Inc.