Mesenchymal stem cell (MSC)-based liver tissue engineering on nanofibrous scaffold holds great promise for cell-based therapy in liver injuries and end-stage liver failure treatments. MSCs were generated from umbilical cord blood. Hepatogenic differentiation was induced on two-dimensional (2D) and three-dimensional (3D) culture system and characterized by morphology, scanning electron microscopy, immunocytochemistry, and gene expression. Albumin and α-1 antitrypsin (AAT) in culture supernatants were measured. Differentiated cells were administered intravenous into a murine model of carbon tetra induced liver cirrhosis. After 12 weeks of injection, liver pathology was examined. The hepatogenic differentiated MSCs stained positively for albumin, alpha fetoprotein, HepPar1, cytokeratin 7 and 18, and OV6 with more mature cells, hexagonal in shape with central nuclei forming large sheets in groups in 3D culture system. AAT secretion and indocyanine green uptake were significantly increased in 3D system. In experimental model, MSC-3D treated group exhibited maximal restoration of liver architecture with absent septal fibrosis and marked improvement of alanine transaminase (ALT) and aspartate transaminase (AST), and mild increase in albumin. Both 3D and 2D culture system are effective in functional hepatogenic differentiation from MSCs and serve as a vehicle in liver tissue engineering. In vivo hepatogenic differentiation is more effective on 3D scaffold, with better functional recovery.

中文翻译：

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在使用肝细胞分化的间充质干细胞的实验模型中诱导肝再生。

纳米纤维支架上的基于间充质干细胞（MSC）的肝组织工程在肝损伤和终末期肝衰竭治疗中的基于细胞的治疗方面具有广阔的前景。MSC由脐带血产生。在二维（2D）和三维（3D）培养系统上诱导肝细胞分化，并通过形态学，扫描电子显微镜，免疫细胞化学和基因表达进行表征。测量培养上清液中的白蛋白和α-1抗胰蛋白酶（AAT）。将分化的细胞静脉内施用至四碳碳诱导的肝硬化的鼠模型中。注射12周后，检查肝脏病理。肝细胞分化的MSC对白蛋白，甲胎蛋白，HepPar1，细胞角蛋白7和18和OV6染色阳性，细胞成熟程度更高，六角形，中心核在3D培养系统中成组形成大片。在3D系统中，AAT的分泌和吲哚菁绿的吸收显着增加。在实验模型中，MSC-3D治疗组表现出最大程度的肝脏结构恢复，无间隔纤维化，丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）明显改善，白蛋白轻度增加。3D和2D培养系统均可有效地从MSC分化为功能性肝细胞，并在肝组织工程中充当载体。MSC-3D治疗组表现出最大程度的肝脏结构恢复，无间隔纤维化，丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）明显改善，白蛋白轻度增加。3D和2D培养系统均可有效地从MSC分化为功能性肝细胞，并在肝组织工程中充当载体。MSC-3D治疗组表现出最大程度的肝脏结构恢复，无间隔纤维化，丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）明显改善，白蛋白轻度增加。3D和2D培养系统均可有效地从MSC分化为功能性肝细胞，并在肝组织工程中充当载体。体内肝发生分化在3D支架上更有效，功能恢复更好。