Vascularization of engineered cardiac tissue

描述（由申请人提供）：在厚的、复杂的组织（如心脏和肝脏）的组织工程中，主要障碍之一是需要在体外使组织血管化。体外血管化可以恢复组织生长过程中的细胞活力，诱导组织结构组织，促进组织植入后的整合。胚胎干细胞具有分化和新生血管形成的能力，这一过程称为血管生成。我们已经证明，当诱导胚胎体形成时，人类胚胎干细胞（hES）可以分化成内皮细胞（ECs），形成血管样结构，并且这些细胞可以被分离并在培养中生长。我们假设hess来源的内皮祖细胞的血管生成潜能可以用于在工程人体组织中诱导血管形成。我们的目标是在三维（3D）聚合物支架上的工程组织结构中诱导血管生成。我们将使用胚胎内皮细胞和心脏细胞的共培养系统，培养在生物可降解聚合物支架上，以满足心脏贴片所需的细胞和机械性能。血管化的结构将被植入并检查与宿主血管系统的整合。我们假设体外形成的血管网络将促进体内组织的血管化。

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.