Myocardial infarction (Ml) is an irreversible injury where sudden interruption of blood flow caused by the occlusion of an artery leads quickly to cardiac myocytes death, loss of tissue and scar formation. Since the self- renewal ability of adult cardiac myocytes is limited, the development of strategies to regenerate damaged myocardium and improve its function represents a major challenge in the treatment of cardiac diseases. Recent evidences have suggested that multipotent somatic stem cells can become reprogrammed in new tissue-specific stem cell niches. However, despite the growing number of observations reporting "trans-differentiation" of adult tissue-derived stem cells, there are no conclusive evidences on the mechanism(s) underlying changes in stem cell fate and sufficient information on the therapeutic potential of these cells. In this proposal we aim to provide a contribution on validation of the use of adult tissue derived stem cells for myocardial repair by: 1) identifying the most suitable adult stem cell type(s) to be used to promote myocardial repair/regeneration; 2) unraveling the combination of stimuli that might drive differentiation of stem cells toward a cardiac myocyte lineage; 3) define genes and factors driving stem cell differentiation into cardiac lineage and set-up safe and effective vectors and protocols to induce cardiac myocyte differentiation pathway(s) by gene transfer; 4) assessing the functional properties of stem cell-derived cardiac myocytes; 5) unraveling the action of factors that might be involved in recruitment and homing of endogenous stem cell in myocardium; 6) evaluating the mid- and long-term effects of stem cell administration by clinical trials of autologous hematopoietic stem cell administration in patients suffering ischemic heart disease.
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