Abstract 2044: Comparative Effects of Mesenchymal Progenitor Cells, Endothelial Progenitor Cells, or their Combination on Myocardial Infarct Regeneration and Cardiac Function
Objectives: Recent evidence indicates that transplanted mesenchymal progenitor cells (MPCs) do not form functional syncytia in the heart and that their effects in myocardial scar may result at least in part from paracrine angiogenesis. We compared and combined the use of MPCs and the angiogenic endothelial progenitor cells (EPCs) for cell-based therapy in a rat infarct model.
Methods: MPCs from bone marrow and EPCs from peripheral blood were isolated from syngeneic donor rats. One million labeled MPCs and EPCs, alone or together, or PBS alone were delivered into the anterior myocardial scar region of 40 rats (N=10 per group) that had undergone left anterior descending artery ligation 21 days earlier. Four weeks after injection, immunohistochemical analysis was performed. Rats also underwent echocardiography immediately prior and four weeks after transplantation.
Results: Labeled cells were detected at 4 weeks within the scar and border regions of myocardium. EPCs, but not MPCs, were observed to express von Willebrand factor and incorporate into the vascular endothelium of capillaries and arterioles. Conversely, evidence of cardiomyocyte differentiation, assessed by troponin T expression, was observed on MPCs but not EPCs. Intercellular connexin43 density, indicative of potential intercellular myocyte communication, was greater in cell-treated groups compared to PBS (by 91.6±8.7%; p<0.001), but no difference was observed between cell groups (p≥0.3). EPC treatment (alone or with MPCs) resulted in increased repopulation of the infarct area with capillaries (by 32% and 24% versus PBS and MPCs alone, respectively; p≤0.03) and fully formed arterioles (by 197% and 66% versus PBS and MPCs alone, respectively; p≤0.02). Compared to baseline, all groups demonstrated continued reductions in left ventricular ejection fraction following treatment (p≤0.02), except the EPC-treated group, which prevented contractile deterioration (p=0.1).
Conclusions: Until myocardial syncytia-forming cell-based strategies are developed and functionally demonstrated, focusing on the transplantation of primarily vasculogenic cells such as the EPC may be an equally viable or potentially superior cell-based approach for the treatment of post-infarct myocardium.