Résumé :
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We have assessed in recent years the utility of different types of progenitors/stem cells for cardiac repair after myocardial infarction. One of the key questions was whether infarcted heart tissue can determine the differentiation fate of engrafted progenitors/stem cells. We found that bone marrow-derived cells do neither transdifferentiate into cardiomyocytes nor endothelial cells using direct injection as well as cytokine-induced mobilization. Furthermore, we identified also adverse effects of this approach, as mesenchymal stem cells did not transdifferentiate into cardiomycytes but rather maintained their potential of osteogenic differentiation. Embryonic stem cells can in contrast to bone marrow-derived cells be differentiated into intact functional cardiomyocytes in vitro. However, injection of undifferentiated ES cells into infarcted hearts of syngeneic mice resulted in large teratomas. We therefore purified with a genetic approach ES cell-derived cardiomyocytes and found that these cells can engraft long term in the infarcted heart and enhance left ventricular function. Moreover, even 3 months after the transplantation no teratomas were detected. Recently, we have also assessed the potential impact of the different progenitors/stem cells on ventricular vulnerability after myocardial infarction and found a protective effect by Cx43 expressing cells. Thus, the heart tissue does not restrict the differentiation fate of progenitors/stem cells injected after myocardial injury.
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