Abstract
Introduction: Human mesenchymal stromal cells (hMSCs) from adipose cardiac tissue have attracted considerable interest for cell-based therapies. However, the best source of hMSCs for infarct repair is still unknown. Hypothesis: We aimed to test the hypothesis that, because of their proximity to the heart, hMSCs from the heart and epicardial fat would be better cells for infarct repair. Methods and Results: We isolated and grew hMSCs from patients with ischemic heart disease (IHD) from four different sources: 1) epicardial fat 2) pericardial fat 3) subcutaneous fat and 4) the right atrium. hMSCs from the right atrium and epicardial fat secreted the highest amounts of trophic and inflammatory cytokines, while hMSCs from pericardial and subcutaneous fat secreted the lowest (p<0.05, n=5-6 per source). Subsequently, the greatest angiogenic effect was induced with conditioned medium from atrium and epicardial fat hMSCs, by tube formation assay. To determine the effect of hMSCs in vivo , we allocated rats to hMSC transplantation 7 days after myocardial infarction (MI) (n=8-10 per group). Atrial hMSCs induced the highest number of vessels in the infarct, together with the highest inflammation score and macrophage accumulation 27 days after their injection. However, left ventricular (LV) dysfunction was worst after therapy with atrium and epicardial fat hMSCs, and minimal after subcutaneous fat hMSC therapy. Notably, there was a correlation between levels of tumor necrosis factor-α and hepatocyte growth factor, in vitro , and post-transplantation LV systolic dilatation. These surprising findings were supported by gene expression analysis in hMSCs from different sources of a patient with IHD. We found that the relative expression of inflammation and fibrosis-related genes was considerably higher in hMSCs from the right atrium and epicardial fat than in subcutaneous fat hMSCs. Conclusions: The origin of hMSCs affects their reparative and immunomodulatory properties. Because of their pro-inflammatory properties, hMSCs from the right atrium and epicardial fat of IHD patients could impair heart function after MI. Our findings might be relevant to autologous MSC therapy and pathogenesis and progression of IHD.
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