Hypothesis: The human injured myocardium does not have ability to regenerate. Cell therapy based on bone marrow-derived autologous progenitor cell mobilization or the exogenous administration of these progenitor cells may be an efficient alternative to conventional medical therapy. Objectives: 1.To study the mobilization, homing and functional implantation of endothelial progenitor cells in patients with and without dilated cardiomyopathy. 2.Induction of differentiation of bone marrow-derived mesenchymal stem cells into cardiomyocytes and characterization of their structural and electrophysiological properties. 3.To develop, with cooperation of myocardiogenic and endothelial progenitors, viable and functionally active myocardial tissue within 3-D polymers and scars from infracted hearts: cardiac tissue engineering. Working plan: extraction and in vitro culture of bone marrow-derived mesenchymal stem cells and circulating endothelial progenitors. Characterization of in vitro vasculogenesis from endothelial progenitors using ad hoc developed microbioreactors. Chemical stimulation, cytokines and growth factors, co-culture and metabolic and physical modulation necessary to transdifferentiate mesenchymal stem cells to mature cardiomyocytes (structurally and electrically). Infarct-derived scars will be cultured in vitro in combination with progenitor endothelial and mesenchymal cells to transdifferentiate the fibrotic tissue into myocardium-like tissue Finally, we will examine the ability to these stem cells to colonize 2-D and 3-D collagen structures in order to create tissue matrices that resemble myocardium, which may have a therapeutic application to regenerate injured hearts
|Effective start/end date||13/12/04 → 13/12/07|
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