Vascularization of engineered cardiac tissue

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DESCRIPTION (provided by applicant): 1 of the major obstacles in tissue engineering of thick, complex tissues (such as the heart and the liver) is the need to vascularize the tissue in vitro. Vascularization in vitro could restore cells viability during growth of the tissue, induce structural organization and promote integration upon implantation. Embryonic stem (ES) cells have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. We have shown that human ES (hES) cells can differentiate into endothelial cells (ECs) forming vascular-like structures when formation of embryoid bodies is induced and that these cells can be isolated and grown in culture. We hypothesize that the vasculogenic potential of hES-derived endothelial progenitors can be used to induce vascularization in engineered human tissue. Our goal will be to induce vasculogenesis in engineered tissue constructs grown on three dimensional (3D) polymer scaffolds. We will use co culture systems of embryonic endothelial and cardiac cells cultured on biodegradable polymer scaffolds designed to meet cellular and mechanical properties needed for a cardiac patch. The vascularized constructs will be implanted and examined for integration with the host vasculature. We hypothesize that the vessel network created in vitro will promote the vascularization of the tissue in vivo.