Decellularized human liver scaffold-based three-dimensional culture system facilitate hepatitis B virus infection

J Biomed Mater Res A. 2019 Aug;107(8):1744-1753. doi: 10.1002/jbm.a.36690. Epub 2019 Apr 24.


Hepatitis B virus (HBV) study is hampered by lacking of idea cell model which support effective HBV infection and meanwhile recapitulate hepatocyte biology function in vivo. In this study, we developed decellularized human liver scaffolds for cell culture and further applied for HBV infection. As a result, primary human hepatocytes (PHHs) engrafted into liver scaffolds and maintained differentiation with stable albumin secretion and liver-specific gene expression. Comparing to mono-layer cell culture, scaffold-based three-dimensional (3D) culture system significantly augment HBV DNA (including cccDNA), RNA level as well as HBsAg secretion. Moreover, HepG2-NTCP cells cultured on 3D system exhibited higher infection efficiency and longer infection period in vitro. In addition, HBV DNA level was suppressed when anti-HBV medicine Entecavir (ETV) introduced into HepG2-NTCP 3D system. Herein, we evaluated the potential of decellularized human liver scaffold-based in 3D cell culture and disclosed that scaffold-based 3D culture system can facilitate HBV infection in vitro. This 3D culture system could be further applied in HBV-related study. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1744-1753, 2019.

Keywords: 3D culture; decellularized human liver scaffold; hepatitis B virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival
  • Hep G2 Cells
  • Hepatitis B / pathology*
  • Hepatitis B virus / metabolism
  • Hepatocytes / cytology
  • Humans
  • Liver / pathology
  • Liver / virology*
  • Liver Cirrhosis / pathology
  • Organic Anion Transporters, Sodium-Dependent / metabolism
  • Phenotype
  • Symporters / metabolism
  • Tissue Culture Techniques*
  • Tissue Scaffolds / chemistry*


  • Organic Anion Transporters, Sodium-Dependent
  • Symporters
  • sodium-bile acid cotransporter