Vascularization of engineered cardiac tissue

描述(申请人提供)：1在厚重、复杂的组织(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。体外血管化可以恢复组织生长过程中的细胞活性，诱导组织结构的形成，促进植入后的整合。胚胎干细胞在一种称为血管生成的过程中具有分化和形成新生血管的能力。我们已经证明，在诱导形成类胚体时，人类ES(HES)细胞可以分化为内皮细胞(ECs)，形成血管样结构，并且这些细胞可以在培养中分离和生长。我们假设HES来源的内皮祖细胞的血管生成潜能可以用来在工程化的人类组织中诱导血管形成。我们的目标将是在三维(3D)聚合物支架上诱导工程化组织结构的血管生成。我们将使用胚胎内皮细胞和心脏细胞的共培养系统，培养在可生物降解的聚合物支架上，旨在满足心脏补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，在体外建立的血管网络将促进体内组织的血管形成。

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.