In vitro and in vivo characteristics of hepatic oval cells modified with human hepatocyte growth factor

Cellular & Molecular Biology Letters

Juan Chen²  Gui-Jie Liu²  Xue-Hua Li²  Xue-Li Zhang²  Zhu Li²  Yan-Chao Gao²  Hiu-Dong Sun²  Zhi-Heng Liu²  Jiang-Hua Ran¹  Li Li¹ 

[1]The First People’s Hospital of Kunming, Kunming, Yunnan, China$$

[2]Department of Hepatobiliary Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong, China$$

关键词: Hepatic oval cells;    Hepatocyte growth factor;    pBLAST2-hHGF;    Plasmid transfection;    Proliferation;    Differentiation;    Liver transplantation;    Rats;    Liver regeneration;   

DOI  :  10.2478/s11658-013-0104-1

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

Hepatocyte growth factor (HGF) is a multifunctional growth factor that controls cell scattering. It has been suggested that it regulates the proliferation of hepatic oval cells (HOCs). Using a HOC line that stably expresses the human HGF gene (hHGF), we investigated the in vitro proliferation and differentiation characteristics of hHGF-modified HOCs and explored their potential capacity for intrahepatic transplantation. A modified 2-acetylaminofluorene and partial hepatectomy (2-AAF/PH) model was established to activate the proliferation of oval cells in the rat liver. HOCs were transfected with the pBLAST2-hHGF plasmid and hHGF-carrying HOCs were selected based on blasticidin resistance. The level of hHGF secretion was determined via ELISA. Cell proliferation was determined using the MTT assay. Differentiation was induced by growth factor withdrawal. A two-cuff technique was used for orthotopic liver transplantation, and HOCs or hHGF-modified HOCs were transplanted into the recipients. The levels of biochemical indicators of liver function were measured after transplantation. An HOC line stably expressing hHGF was established. The transfected line showed greater hHGF secretion than normal HOCs. The hHGF gene promoted the proliferation capability of HOCs by reducing the peak time in vitro. The hHGF-modified HOCs differentiated into hepatocytes and bile duct epithelial cells upon growth factor withdrawal in vitro. In addition, hHGF-modified HOC transplantation significantly prolonged the median survival time (MST) and improved the liver function of recipients compared to HOC transplant recipients and nontransplanted controls. Our results indicate that hHGF-modified HOCs may have valuable properties for therapeutic liver regeneration after orthotopic liver transplantation.

【 授权许可】

Unknown