iPS细胞在组织工程心肌构建中的应用基础研究

项目名称： iPS细胞在组织工程心肌构建中的应用基础研究

项目编号： No.31271039

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 郑强荪

作者单位： 中国人民解放军第四军医大学

项目金额： 80万元

中文摘要： 心肌细胞由于增殖能力差且来源受限，不适宜作为组织工程心肌构建的种子细胞。如何寻求合适的种子细胞是目前迫切需要解决的问题。iPS细胞源于体细胞重编程，具有多向分化潜能且避免了伦理及免疫排斥问题，是比较理想的种子细胞来源。但iPS细胞分化效率低下，不足以制备大批量的种子细胞。我们前期研究中建立了心肌分化与组织工程心肌构建的优势平台。本研究拟利用aMHC-eGFP转基因小鼠建立携带心肌分化报告基因的iPS细胞系，实时追踪iPS细胞的心肌分化过程；在3D共培养诱导体系下，探索Integrin信号途径调控iPS细胞心肌分化的机制，从而高效地诱导iPS细胞向心肌细胞分化。通过脱细胞基质支架种植iPS细胞来源的心肌细胞，联合组织化培养进行组织工程心肌构建的初步研究，评价iPS细胞应用价值。本研究旨在探讨iPS细胞在组织工程心肌构建中的作用及其心肌再生机理，为心肌梗死患者的心肌修复治疗提供新的理论依据。

中文关键词： iPS细胞；心肌细胞分化；信号通路；组织工程心肌；纳米支架

英文摘要： Because of limited source and insufficient number of the primary cardiomyocytes, the tissue-engineered heart using the primary cardiomyocytes as seed cells was failure to be applied to clinic. The IPS cells induced from adult fibroblast were regarded as proper seed cells for their pluripotent without ethics dispute and immunity rejection reaction. However, the differentiating efficiency from iPS cell is low. We previously have built up a good platform of cardiac differentiation and cardiac tissue engineering. In this study, we establish a new iPS cell line containing a cardiac differentiation report gene from the aMHC-eGFP transgenic mice, to monitor the cardiac differentiation from iPS cell. By using a novel 3D co-culture mode, we try to find the mechaniasm of the integrin signaling regulating this differentiation to improve the differentiation rate of IPS efficiently. An acellular matrix obtained from adult heart was used as a scaffold. We use the iPS cell-derived cardiomyocytes as seed cells to construct tissue-engineered myocardium in a biological reactor by cyclical perfusion culture and neovascularization techniques. The aim of this study is to investigate the use of iPS cell in cardiac tissue engineering. We try to get the knowledeg of the mechanism in cardiac regeneration and provide the new idea about t

英文关键词： iPS cells；Cardiomyocyte differentiation；Signal pathway；Cardiac tissue engineering；Nanofibrous scaffold