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

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

Zhang Z1,2,3,4, Xu H1,2,3,4, Mazza G5, Zhang M6, Frenguelli L5, Liu Q1,2,3,4, Al-Akkad W5, Ren J7,8, Zhao R1,2,3,4, Ren F7,8, Chen X1,2,3,9, Huang A7,8, Chen J7,8.

Author information

1
Ministry of Education Key Laboratory of Child Development and Disorders, ChongQing, China.
2
Key Laboratory of Pediatrics in Chongqing, Chongqing, China.
3
Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
4
Department of Infectious Disease, Children's Hospital of ChongQing Medical University, ChongQing, China.
5
UCL Institute for Liver and Digestive Health, Royal Free Hospital, University College London, London, United Kingdom.
6
Department of Hepatobiliary Surgery, Children's Hospital of ChongQing Medical University, ChongQing, China.
7
The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, ChongQing, China.
8
Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, ChongQing, 400016, China.
9
The General Gard, Children's Hospital of ChongQing Medical University, ChongQing, China.

Abstract

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.

KEYWORDS:

3D culture; decellularized human liver scaffold; hepatitis B virus

PMID:
30963688
DOI:
10.1002/jbm.a.36690

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