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"Liver-on-a-Chip" Cultures of Primary Hepatocytes and Kupffer Cells for Hepatitis B Virus Infection
Published on: February 19, 2019
Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures
Alexander Ploss1, Salman R Khetani, Christopher T Jones
1Center for the Study of Hepatitis C and Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10065, USA.
Summary
A new micropatterned co-culture system fully replicates the Hepatitis C virus (HCV) life cycle. This breakthrough offers a promising platform for developing effective antiviral therapies and assessing drug toxicity for Hepatitis C virus (HCV).
Area of Science:
- Virology
- Hepatology
- Drug Discovery
Background:
- Hepatitis C virus (HCV) poses a significant global health challenge, infecting millions and causing severe liver disease.
- Current preventative and therapeutic strategies for HCV are limited, with no vaccine available and existing treatments often ineffective.
- The absence of reliable cell culture models that predict human responses has hindered the development of targeted antiviral drugs.
Purpose of the Study:
- To establish a robust in vitro model system that recapitulates the entire Hepatitis C virus (HCV) life cycle.
- To develop a high-throughput platform for evaluating the efficacy and toxicity of potential anti-HCV therapeutics.
Main Methods:
- Utilized micropatterned co-cultures (MPCCs) comprising primary human hepatocytes and supportive stromal cells in a multiwell format.
- Characterized the MPCCs for polarization, expression of HCV entry factors, and sustained viral replication.
- Integrated sensitive fluorescence- and luminescence-based reporter systems for drug screening.
Main Results:
- Successfully recapitulated the complete Hepatitis C virus (HCV) life cycle within the MPCC system.
- MPCCs formed polarized cell layers that sustained HCV replication for extended periods.
- The system demonstrated potential for high-throughput screening of anti-HCV agents.
Conclusions:
- Micropatterned co-cultures (MPCCs) provide a novel and effective in vitro model for studying the Hepatitis C virus (HCV) life cycle.
- This platform facilitates the simultaneous assessment of antiviral efficacy and drug toxicity, accelerating the development of new Hepatitis C virus (HCV) treatments.
