去细胞化支架内诱导多潜能干细胞来源的特定双胚层细胞重建肝样组织的机制研究

项目名称： 去细胞化支架内诱导多潜能干细胞来源的特定双胚层细胞重建肝样组织的机制研究

项目编号： No.81470874

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张启瑜

作者单位： 温州医科大学

项目金额： 73万元

中文摘要： 慢性肝纤维化及其伴随的慢性肝功能衰竭、门静脉高压症是一直困扰临床的待解问题，干细胞来源的可移植性组织工程化肝脏可能是最终治愈此疾病的技术。本团队拟于肝去细胞化支架培养系统内以诱导多潜能干细胞（iPSc）来源的特定中胚层和内胚层细胞诱导共培养模式在体外重建肝样组织。通过MICRO-CT、全基因组表达谱芯片、活体动物荧光成像仪和荧光成像系统等方法较全面的记录和评价诱导过程中肝细胞成熟程度、内皮系统重建程度、胆汁分泌系统再生程度等指标；证实诱导培养的肝样组织获得类肝的结构和功能重建；并从肝脏发育、再生的特异性核心信号通路及肝再生因子分泌角度揭示其诱导重建机制。进一步体内移植肝样组织，验证其结构和功能重建程度，为下一步的人可移植肝脏组织的制备及临床治疗提供前期基础研究支持。

中文关键词： 去细胞化支架；可移植肝组织；诱导多潜能干细胞；内胚层细胞；中胚层细胞

英文摘要： It has been for a long time that the chronic liver fibrosis which can cause chronic liver failure, portal hypertension became an obsessing problem in clinical practicing. Stem cell derived transplantable liver tissue may be the ultimate way to cure such disease. Our team plans to reconstruct the hepatic-like tissue in-vitro by inducing both the defined mesoderm and endoderm cells which are co-cultured in a decellularized scaffold culture system. Using the MICRO-CT, Whole Genome Expression Microarray, Optical in vivo Imaging, Fluorescence Imaging System and other methods to make a comprehensive evaluation of hepatic maturity, endothelial system reconstruction and bile duck regeneration in this hepatic-like tissue, we can ascertain whether this liver regeneration method promotes the formation and maturation of hepatic-like tissue, and to unveil the mechanism concerning the aspects of specifically core signaling pathways of liver development and regeneration. Moreover, we testify the rebuilt of the structure and function through in vivo liver transplantation experiments. All the results can preliminary support the basic research of human-scale transplantable liver tissue.

英文关键词： Decellularized scaffold;Transplantable liver tissue;induced Pluripotent Stem cells;Entoderm cells;Mesoderm cells