Vascularization of engineered cardiac tissue

描述（由申请人提供）：厚的复杂组织（如心脏和肝脏）的组织工程中的主要障碍之一是需要在体外使组织血管化。体外血管化可以在组织生长期间恢复细胞活力，诱导结构组织化并促进植入后的整合。胚胎干细胞（ES）具有在称为血管发生的过程中分化和从头形成血管的能力。我们已经表明，人ES（hES）细胞可以分化成内皮细胞（EC）形成血管样结构时，诱导胚状体的形成，这些细胞可以分离和培养生长。我们假设，hES衍生的内皮祖细胞的血管生成潜力可用于诱导工程化的人体组织中的血管形成。我们的目标是在三维（3D）聚合物支架上生长的工程组织构建中诱导血管发生。我们将使用胚胎内皮细胞和心脏细胞的共培养系统，在可生物降解的聚合物支架上培养，以满足心脏补片所需的细胞和机械性能。将植入血管化结构并检查其与宿主血管系统的整合。我们假设，在体外创建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.