诱导型多能干细胞（iPSC）在肝脏全器官脱细胞基质中的分化、发育及其分子机制研究

项目名称： 诱导型多能干细胞（iPSC）在肝脏全器官脱细胞基质中的分化、发育及其分子机制研究

项目编号： No.31200734

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 邱丽媛

作者单位： 中国人民解放军军事医学科学院

项目金额： 22万元

中文摘要： 肝脏疾病严重危害人类健康。近年来，基于全器官脱细胞-再细胞化策略的肝脏再造研究进展迅速。已有报道表明，iPSC可以分化为肝细胞，但肝脏全器官脱细胞基质微环境对iPSC分化与发育的影响则尚未见报道。本项目拟首先摸索肝脏全器官脱细胞的条件与规律，并以iPSC为种子细胞进行肝脏全器官脱细胞基质的再细胞化，通过单纯iPSC移植以及在培养基中添加不同诱导分化条件，深入研究iPSC在肝脏全器官脱细胞基质中分化并形成肝组织的能力，探索以iPSC为种子细胞，利用肝脏全器官脱细胞基质体外再造肝脏的可行性。在此基础上，深入研究在不同的肝脏全器官脱细胞基质条件下，iPSC所处脱细胞基质局部微环境以及体内外环境影响其向肝细胞分化、发育的规律及分子机制。本研究有望为利用iPSC为种子细胞进行肝脏再造提供重要实验数据。此外，再造的肝脏组织在未来肝脏疾病治疗、各类肝脏药物的筛选、药物毒性评价等方面均具有潜在的应用前景。

中文关键词： 肝脏组织工程；支架材料；脱细胞基质；大网膜；ips再细胞化

英文摘要： Liver disease threaten human health severly. In recent years, the strategy of whole organ decellularization- recellularization based liver reconstruction has been progressing rapidly. It has been reported that iPSCs could differentiate into hepatocytes, but no report are available about the influence of decellularized whole liver matrix on the differentiation and development of iPSCs. This progect intend to explore the conditions and laws for the whole liver decellularization at first. Then,iPSCs were used as seeding cells to recellularize the decellularized whole-liver matrix. IPSCs in matrix were cultured with or without inducers, exploring the capacity of iPSCs to differentiate into hepatocytes and form liver tissues in the decellularized whole-liver matrix as well as the feability to reconstruct liver using iPSCs and the matrix. On this basis, by seeding iPSCs in different decellularized liver matrix, the laws and molecular mechanisms about how the in vivo and in vitro local microenvironments influence the hepatic differentiation of iPSCs was deeply investigated. This study is expected to provide important experimental data for liver reconstruction using iPSCs as seeding cells. In addition, the reconstructed liver tissue is of potential application in the treatment of liver diseases, screening drugs of live

英文关键词： Liver tissue engineering；Scaffold；Decellularized matrix；Greater Omentum；iPS recellularization