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Hepatocyte-like cells derived from induced pluripotent stem cells: A versatile tool to understand lipid disorders

  • Lars E. Larsen
    Affiliations
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
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  • Mikhaila A. Smith
    Affiliations
    Departments of Genetics and Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
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  • Deepti Abbey
    Affiliations
    Departments of Genetics and Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
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  • Amber Korn
    Affiliations
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands

    Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
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  • Laurens F. Reeskamp
    Affiliations
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands

    Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
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  • Nicholas J. Hand
    Correspondence
    Corresponding author. Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Smilow Building, SCTR 11-135, Philadelphia, PA, 19104, USA.
    Affiliations
    Departments of Genetics and Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
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  • Adriaan G. Holleboom
    Correspondence
    Corresponding author. Department of Vascular Medicine, Academic Medical Center, Meibergdreef 15, 1105 AZ, Amsterdam, the Netherlands.
    Affiliations
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands

    Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
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      Highlights

      • Hepatocyte like cells (HLCs) can provide an in vitro hepatic cell line with specific variants without gene editing tools.
      • HLCs provide a versatile tool for investigating lipid/lipoprotein metabolism in vitro.
      • HLCs provide a platform to test the biological impact of genetic variants compared to an isogenic control.
      • HLCs provide a platform for high throughput drug testing.

      Abstract

      Dyslipidemias are strongly linked to the development of atherosclerotic cardiovascular disease. Most dyslipidemias find their origin in the liver. In recent years, the differentiation of induced pluripotent stem cells (iPSCs) into hepatocyte-like cells has provided a versatile platform for the functional study of various dyslipidemias, both rare genetic dyslipidemia as well as common lipid disorders associated with insulin resistance or non-alcoholic fatty liver disease. In addition, iPSC-derived hepatocytes can serve as a cell model for developing novel lipid lowering therapies and have the potential of regenerative medicine. This review provides an overview of these developments.

      Keywords

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