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


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.







alkaline phosphate


alanine aminotransferase




direct bilirubin


epidermal growth factor


enzyme-linked immunoassay




hepatocyte growth factor


human hepatocyte growth factor


hepatic oval cells




leukemia inhibitory factor


median survival time


partial hepatectomy


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Correspondence to Zhu Li.

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Zhu Li and Juan Chen contributed equally to this study

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Li, Z., Chen, J., Li, L. et al. In vitro and in vivo characteristics of hepatic oval cells modified with human hepatocyte growth factor. Cell Mol Biol Lett 18, 507–521 (2013).

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Key words

  • Hepatic oval cells
  • Hepatocyte growth factor
  • pBLAST2-hHGF
  • Plasmid transfection
  • Proliferation
  • Differentiation
  • Liver transplantation
  • Rats
  • In vitro
  • Liver regeneration