Long-term 3D cell culture models for hepatitis B virus studies

Area of Science:

• Hepatology
• Virology
• 3D Cell Culture Technology

Background:

• Primary human hepatocyte (PHH) models for Hepatitis B virus (HBV) research suffer from limited longevity and require high viral loads.
• Existing models present challenges for extensive drug-related studies and understanding HBV pathogenesis.

Purpose of the Study:

• To develop advanced 3D cell culture models for HBV infection that overcome the limitations of current PHH models.
• To enhance the longevity and utility of HBV infection models for drug discovery and in vitro research.

Main Methods:

• Establishment of two spheroid models using de novo HBV-infected mouse-passaged (mp)PHH and HBV-infected liver chimeric mouse-derived mpPHH (HBV-mpPHH).
• Characterization of model longevity, HBV infection levels, and human albumin production over time.
• Proof-of-concept drug testing using the de novo HBV-infected model to validate an HBV capsid assembly modulator (CpAM).

Main Results:

• The developed 3D spheroid models maintained detectable HBV infection and human albumin levels for up to 75 days, demonstrating enhanced longevity.
• The models proved effective as a drug-testing platform, successfully validating an HBV CpAM.
• The models represent a practical and novel approach for in vitro HBV studies.

Conclusions:

• Two novel HBV-infected 3D spheroid cell culture models have been successfully established.
• These models offer enhanced longevity and utility compared to existing PHH models for HBV research.
• The developed models hold significant potential to advance in vitro studies in HBV drug discovery and pathogenesis.