Biopolymer-guided human stem cell assembly for engineered myocardium

描述（由申请人提供）： 组织工程中的关键需求是在相对厚的和/或代谢工程化的组织（例如工程化心肌）内产生微脉管系统的等同物的手段。该提议结合了使用来自方便的自体来源的干细胞和通过细胞截留和随后将纤维蛋白凝胶重塑成对齐组织的引导细胞组装技术，以创建可灌注和跳动的工程化心肌。可灌注组织构建体将由血液生长内皮细胞和周细胞制成。搏动组织构建体将由诱导多能干细胞（iPS）衍生的心肌细胞制造。可灌注和跳动的工程化心肌将通过使用相同的引导细胞组装方法共包埋三种细胞类型来制造，该方法基于机械约束的细胞收缩和纤维蛋白凝胶的对齐。这些组织构建体将在体外进行广泛表征，然后在梗死大鼠心脏模型中进行评估，以改善功能结局。这项研究的结果将使许多工程组织的技术成为可能-一种创造功能性微血管系统的手段-以及功能性心脏补丁的基础，可以治疗心肌梗死并可能预防充血性心力衰竭的发作。 (End摘要）

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)