Biopolymer-guided human stem cell assembly for engineered myocardium

生物聚合物引导的人类干细胞组装用于工程化心肌

• 批准号: 8328585
• 负责人: ROBERT T TRANQUILLO
• 金额: $ 74.44万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-05 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8328585
• 关键词: Affect; Autologous; Biopolymers; Bioreactors; Blood; Cardiac; Cardiac Myocytes; Cells; Cellular Structures; Cellularity; Characteristics; Collagen; Congestive Heart Failure; Contracts; Data; Deposition; Development; Dyes; Endothelial Cells; Engineering; Extracellular Matrix; Fiber; Fibrin; Fibroblasts; Gel; Generations; Generic Drugs; Goals; Heart; Heart failure; Human; Hypertrophy; Implant; In Vitro; Infarction; Knowledge; Measures; Mechanics; Metabolic; Methods; Modeling; Monitor; Myocardial Infarction; Myocardium; Neonatal; Nude Rats; Oxygen; Patients; Perfusion; Pericytes; Phenotype; Property; Rattus; Research; Screening procedure; Source; Stem cells; Stretching; System; Technology; Thick; Time; Tissue Engineering; Tissues; Tracer; Tube; Umbilical vein; Venous; abstracting; base; cell assembly; cell type; design; functional outcomes; human stem cells; improved; induced pluripotent stem cell; interstitial; prevent; reconstitution; research study; self assembly; success; tissue culture

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)

描述（由申请人提供）： 组织工程的一个关键需求是在相对较厚和/或代谢工程组织（例如工程心肌）内创建相当于微脉管系统的方法。该提案结合了使用方便的自体来源的干细胞和通过细胞捕获和随后将纤维蛋白凝胶重塑成排列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。可灌注的组织构建体将由血液生长的内皮细胞和周细胞制成。跳动组织构建体将由诱导多能干细胞（iPS）衍生的心肌细胞制成。然后，将使用相同的引导细胞组装方法，通过共同捕获三种细胞类型来制造可灌注和跳动的工程心肌，该方法基于机械约束的细胞收缩和纤维蛋白凝胶的排列。这些组织结构将在体外进行广泛的表征，然后在梗塞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支持技术（一种创建功能性微脉管系统的方法），也为功能性心脏补片的基础，该补片可以治疗心肌梗塞并有可能预防充血性心力衰竭的发生。 （摘要完）