Related Experiment Video
Updated: May 5, 2026
Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery
Published on: May 19, 2018
Hepatic cells derived from induced pluripotent stem cells of pigtail macaques support hepatitis C virus infection
Marion Sourisseau1, Orit Goldman, Wenqian He
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York.
Abstract:
The narrow species tropism of hepatitis C virus (HCV) limits animal studies. We found that pigtail macaque (Macaca nemestrina) hepatic cells derived from induced pluripotent stem cells support the entire HCV life cycle, although infection efficiency was limited by defects in the HCV cell entry process. This block was overcome by either increasing occludin expression, complementing the cells with human CD81, or infecting them with a strain of HCV with less restricted requirements for CD81. Using this system, we can modify viral and host cell genetics to make pigtail macaques a suitable, clinically relevant model for the study of HCV infection.
Insights
Researchers developed a new model using pigtail macaque liver cells to study hepatitis C virus (HCV) infection. This breakthrough overcomes previous limitations, enabling better research into HCV treatments.
Area of Science:
- Hepatology
- Virology
- Stem Cell Biology
Background:
- Hepatitis C virus (HCV) exhibits narrow species tropism, significantly hindering the development of effective animal models for studying the infection.
- Existing animal models do not fully recapitulate the human disease, limiting research into pathogenesis and therapeutic interventions.
Purpose of the Study:
- To establish a novel in vitro model system using pigtail macaque hepatic cells to study the complete hepatitis C virus (HCV) life cycle.
- To overcome the limitations of HCV cell entry in the established macaque model and facilitate its use for preclinical studies.
Main Methods:
- Generation of hepatic cells from induced pluripotent stem cells of pigtail macaques (Macaca nemestrina).
- Assessment of the entire HCV life cycle in these derived cells.
- Overcoming cell entry barriers by manipulating occludin expression, introducing human CD81, or using adapted HCV strains.
Main Results:
- Pigtail macaque hepatic cells derived from induced pluripotent stem cells support the complete HCV life cycle.
- HCV infection efficiency was initially limited by defects in the cell entry process.
- Increasing occludin expression, complementing with human CD81, or using a less restricted HCV strain successfully overcame the entry block.
Conclusions:
- The developed pigtail macaque hepatic cell system supports the entire HCV life cycle, offering a promising preclinical model.
- Modifications to viral and host cell genetics can render pigtail macaques a clinically relevant model for hepatitis C virus research.
- This advancement facilitates the study of HCV infection and the evaluation of novel therapeutic strategies.
