Engineered Anisotropic and Vascularized Human Cardiac Patch

工程化各向异性血运人体心脏补片 项目摘要 目前尚无有效逆转心肌梗死后心脏损伤的治疗方法。 组织工程为通过工程心脏补片再生心脏组织提供了希望。 不幸的是，以前的努力未能实现具有有效植入率的心脏补片和 再生功效。人多能干细胞来源的心脏成纤维细胞(hPSCs-CFs)具有 为了提供无限的心脏组织特异性细胞外基质(ECM)，可以组织 变成纳米纤维，作为一种通用的支架来指导细胞的各向异性取向和工程化 将微血管转化为仿生的层级结构。人间充质干细胞(HMSCs) 免疫调节和有效促进心肌再生，并可作为周细胞功能，以 由内皮细胞构建的成熟和稳定的微血管。人多能干细胞来源 心肌细胞(hPSCs-CMS)可以协调移植心肌组织之间的收缩同步性 和下面的心肌。我们假设hPSCs-CF来源的心脏组织的组合- 含有hMSCs和毛细血管的特定ECM纳米纤维将显著增强各向异性 心脏组织植入，有效促进心肌再生。建议的目标是 该项目是以生物仿生技术设计一种各向异性心脏贴片，该贴片包含特定排列的心脏组织 纳米纤维状细胞外基质、致密定向的毛细血管样微血管、收缩的CMS和促进再生 在短时间内培养人骨髓间充质干细胞。拥有一支由知名组织工程师组成的强大团队，世界 领先的心血管内科医生兼科学家，非常有经验的心血管生理学家， 电生理学和光学测绘，以及一位经验丰富的生物统计学家，我们将追求的具体目标：I. 从hPSC-CFs中衍生出排列整齐的心脏特异性纳米纤维ECM支架。二、制定 代表天然心肌的各向异性、血管化和收缩的心脏补片。三、评估 预钙化心脏补片在大鼠心肌梗死模型中的吻合、植入和再生效果。

Engineered Anisotropic and Vascularized Human Cardiac Patch Project Summary Currently there are no therapies to effectively reverse cardiac injury following myocardial infarction. Tissue Engineering holds promise for the regeneration of heart tissue through an engineered cardiac patch. Unfortunately, pervious efforts have failed to achieve a cardiac patch with an effective engraftment rate and regenerative efficacy. Human pluripotent stem cell-derived cardiac fibroblasts (hPSCs-CFs) have the potential to provide an unlimited supply of cardiac tissue-specific extracellular matrix (ECM), which could be organized into nanofibers and serve as a universal scaffold to direct the anisotropic orientation of cells and engineered microvessels into a biomimetic hierarchical structure. Human mesenchymal stem cells (hMSCs) are immunomodulatory and effective in promoting myocardial regeneration, and can function as pericytes to mature and stabilize microvessels constructed by endothelial cells. Human pluripotent stem cell-derived cardiomyocytes (hPSCs-CMs) could orchestrate contractile synchrony between the transplanted cardiac tissue and the underlying myocardium. We hypothesize that the combination of hPSCs-CF derived cardiac tissue- specific ECM nanofibers with hMSCs and capillary-like microvessels will significantly enhance the anisotropic cardiac tissue engraftment and effectively promote myocardial regeneration. The objective of the proposed project is to biomimetically engineer an anisotropic cardiac patch containing aligned cardiac tissue-specific nanofibrous ECM, dense and oriented capillary-like microvessels, contractile CMs, and regeneration-promoting hMSCs within a short time. With a strong team comprising of a well-established tissue engineer, a world leading cardiovascular physician-scientist, a very experienced cardiovascular physiologist, an expert in electrophysiology and optical mapping, and an experienced biostatistician, we will pursue the specific aims: I. Derive an aligned and uniform cardiac-specific nanofibrous ECM scaffold from hPSC-CFs. II. Develop an anisotropic, vascularized and contractile cardiac patch representative of native myocardium. III. Evaluate the anastomosis, engraftment and regeneration efficacy of the prevascualrized cardiac patch in a rat MI model.