Engineered Anisotropic and Vascularized Human Cardiac Patch

工程化各向异性和血管化人类心脏补片 项目摘要 目前还没有有效逆转心肌梗死后心脏损伤的治疗方法。 组织工程有望通过工程心脏补片再生心脏组织。 不幸的是，先前的努力未能获得具有有效植入率和植入时间的心脏补片。 再生效能人多能干细胞来源的心脏成纤维细胞（hPSCs-CFs）具有潜在的 提供无限量的心脏组织特异性细胞外基质（ECM）， 纳米纤维，并作为一个通用的支架，以指导细胞的各向异性取向和工程 将微血管转化为仿生层次结构。人骨髓间充质干细胞（hMSCs） 免疫调节和有效促进心肌再生，并可作为周细胞， 成熟和稳定由内皮细胞构建的微血管。人多能干细胞衍生 心肌细胞（hPSCs-CMs）可以协调移植心脏组织之间的收缩同步性， 和底层心肌我们假设hPSC-CF衍生的心脏组织的组合- 具有hMSC和毛细血管样微血管的特定ECM纳米纤维将显著增强细胞的各向异性。 心脏组织植入，有效促进心肌再生。建议的目标 项目是生物仿生工程的各向异性心脏补丁含有对齐的心脏组织特异性 纳米纤维状ECM、致密和定向的毛细血管样微血管、收缩性CM和再生促进 hMSCs在短时间内凭借由知名组织工程师组成的强大团队， 领先的心血管内科医生，科学家，一个非常有经验的心血管生理学家，专家， 电生理学和光学映射，和一个有经验的生物统计学家，我们将追求的具体目标：I。 从hPSC-CF衍生对齐且均匀的心脏特异性纳米纤维ECM支架。二.开发一个 代表天然心肌的各向异性的、血管化的和收缩的心脏片。三.评价 在大鼠MI模型中预血管化心脏补片的吻合、植入和再生功效。

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.