Biopolymer-guided human stem cell assembly for engineered myocardium

描述(由申请人提供)： 组织工程学中的一个关键需求是一种在相对较厚和/或代谢工程化组织(如工程化心肌)中创建相当于微血管系统的方法。该方案结合了使用方便的自体来源的干细胞和通过细胞包裹和随后将纤维蛋白凝胶重塑为排列的组织来引导细胞组装的技术，以创建可灌流和跳动的工程化心肌。可灌流的组织结构将由血液长出的内皮细胞和周细胞构成。搏动组织结构将由诱导多能干细胞(IPS)来源的心肌细胞构建而成。然后，通过使用相同的引导细胞组装方法，基于机械约束的细胞收缩和纤维蛋白凝胶的排列，通过共包裹三种类型的细胞来构建可灌流和跳动的工程化心肌。这些组织结构将在体外广泛表征，然后在梗死大鼠心脏模型中进行评估，以改善功能结果。这项研究的结果既将为许多工程组织提供技术支持--一种创造功能微血管的手段--也将为治疗心肌梗死并潜在地预防充血性心力衰竭的功能性心脏贴片奠定基础。(摘要结束)

DESCRIPTION (provided by applicant): A critical need in tissue engineering is a means to create the equivalent of a microvasculature within relatively thick and/or metabolic engineered tissues, such as engineered myocardium. This proposal combines the use of stem cells from convenient autologous sources and the technology of guided cell assembly via cell entrapment in and subsequent remodeling of fibrin gel into aligned tissue in order to create a perfusable and beating engineered myocardium. Perfusable tissue constructs will be fabricated from blood outgrowth endothelial cells and pericytes. Beating tissue constructs will be fabricated from induced pluripotent stem cell (iPS)-derived cardiomyocytes. Perfusable and beating engineered myocardium will then be fabricated by co-entrapment of the three cell types using the same guided cell assembly methods, which are based on mechanically-constrained cell contraction and alignment of fibrin gel. These tissue constructs will be extensively characterized in vitro and then assessed in an infarcted rat heart model for improved functional outcomes. The results from this research will be both enabling technology for many engineered tissues - a means to create a functional microvasculature - and the basis for a functional heart patch that can treat myocardial infarcts and potentially prevent onset of congestive heart failure. (End of Abstract)