中文摘要：

人骨髓间充质干细胞（hBMSCs）源的肝细胞对于肝脏疾病的治疗和药物的开发具有巨大的应用潜力。利用基因工程技术构建了融合蛋白质粒，并通过真核细胞表达体系表达出了人E-钙粘素胞外域与免疫球蛋白Fc段的融合蛋白（hE—eadherin—Fe），并将其用于疏水材料的表面修饰仿生构建细胞-细胞间相互作用的细胞外微环境，检测其对hBMSCs向肝样细胞定向诱导分化的影响。诱导分化培养4周后，与组织培养板（TC-PS）、明胶（Gelatin）基质相比，hE—eadherin-Fe基质显著促进细胞表达ALB、CKl8、HNF-4等肝细胞分化基因，并且细胞的糖原合成和吲哚青绿（ICG）摄取功能均显著提高。在hE—eadherin—Fc基质表面分化培养4周时，白蛋白和尿素合成的量为2．7pg／细胞／d和36．7Pg／细胞／d，相对于TC—PS和Gelatin分别提高了42．1％和28．6％、57．5％和25．7％。综上所述，利用hE—eadherin—Fe基质化构建细胞外微环境，有利于促进人骨髓间充质干细胞向功能化肝细胞的定向分化。

英文摘要：

Hepatocytes differentiating from human mesenehymal stem cells （hBMSCs） hold great potentials for cell-based approaches to liver diseases and drug development. In order to effectively expand and induce hepatic differentiation of hBMSCs, a fusion protein consisting of human E-cadherin extracellular domain and the immunoglohulin G Fc region （hE-cadherin-Fc） was biosynthesized and used as an extracellular matrix biomimicking epithelia cell adhesion junction. The effects of the hE-cadherin-Fc matrix on the hepatic differentiation of hBMSCs were studied in this paper. Compared with TC-PS and gelatin coated surfaces, the hE-cadherin-Fc matrix effectively stimulated the hBMSCs to progress toward the polygonal morphology of hepatocyte, and enhanced the differentiated ceils expressing hepatocyte-specific genes and live-specific functions. These results show hE-cadherin-Fc is a promising artificial extracellular matrix （ECM） for the hBMSCs differentiation via homophilic interaction of hE-cadherin and synergy between cell adhesion molecular and growth factors.