仿肝板结构肝组织三维培养恢复并维持肝细胞极性的机制研究

项目名称： 仿肝板结构肝组织三维培养恢复并维持肝细胞极性的机制研究

项目编号： No.81470875

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： 高毅

作者单位： 南方医科大学

项目金额： 73万元

中文摘要： 如何利用生物反应器在体外培养中长时间维持肝细胞的表型和分化功能是生物人工肝目前面临的关键问题。极性是肝细胞功能的基础，我们通过借鉴肝细胞在肝脏的极性肝板排列，以及其与非实质细胞、细胞外基质相互作用的仿生学原理，提出仿肝板结构肝组织三维培养技术研究课题，认为仿肝板结构三维培养有助于重建和维持肝细胞极性从而使肝细胞在体外培养中具备更接近于体内细胞的表型和分化功能。本项目拟利用微流控芯片技术在体外构建仿肝板结构肝组织，通过对这种培养模式下肝细胞功能进行测定并与其他体外培养模式相比较，以期得到新的适于生物人工肝应用的体外肝细胞培养模式以及新型生物反应器。同时对肝细胞极性变化进行测定，探究体外培养肝细胞极性重建的机制以及细胞功能与极性重建之间的关系，一方面为体外肝细胞极性重建研究提供指导依据，另一方面也为生物人工肝、细胞移植治疗、肝脏病理生理等进一步研究奠定基础。

中文关键词： 生物人工肝；生物反应器；仿生学；三维培养；肝细胞极性

英文摘要： Nowadays, bioartificial liver is faced with the main problem that how hepatocytes can maintain hepatocyte phenotype and differentiated functions when cultured in vitro for long time by taking advantage of bioreactors. Hepatocyte polarity is the foundation of hepatic functions. And hepatocytes are arranged into the polarized hepatic plate structure and attain cell-cell and cell-matrix interactions within a liver. Based on the bionics, we propose the project of three-dimensional culture of liver tissue mimicking the hepatic plate structure. We conclude that liver tissue mimicking the hepatic plate structure contributes to the recovery and maintenance of hepatocyte polarity so that hepatocyte phenotype and differentiated functions in vitro will be much more resemble to the state in vivo. We are planning to construct human liver tissue mimicking the hepatic plate structure by means of microfluidic chip. Compared with the other culture patterns, we measure their hepatic functions to find a novel three-dimensional culture pattern in vitro and bioreactor that is proper to the application of bioartificial liver. Meanwhile we study the hepatocyte polarity changes to investigate the mechanism that how three-dimensional culture of liver tissue mimicking the hepatic plate structure reconstructs hepatocyte polarity and relationship between function and reconstruction of polarity. Based on the above research, we can provide guidelines for the reconstruction of hepatocyte polarity in vitro and lay a solid foundation for bioartificial liver, treatment by transplantation of hepatocyte, and study of liver pathology and physiology.

英文关键词： bioartificial liver;bioreactor;bionics;three-dimensional culture;hepatocyte polarity