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Updated: Mar 20, 2026

"Liver-on-a-Chip" Cultures of Primary Hepatocytes and Kupffer Cells for Hepatitis B Virus Infection
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A Microfabricated Platform for Generating Physiologically-Relevant Hepatocyte Zonation.

William J McCarty1, O Berk Usta1, Martin L Yarmush1

  • 1Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children-Boston, Boston, MA, USA.

Scientific Reports
|June 1, 2016
PubMed
Summary
This summary is machine-generated.

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Researchers created controlled metabolic zonation in liver cells using microfluidic devices. This breakthrough improves in vitro liver models for drug metabolism and toxicity testing.

Area of Science:

  • Hepatology
  • Biotechnology
  • Toxicology

Background:

  • In vitro liver models are crucial for research and drug toxicity screening.
  • Hepatocytes exhibit metabolic zonation based on their position in the liver sinusoid.
  • Replicating this metabolic zonation in vitro is often overlooked but vital for accurate models.

Purpose of the Study:

  • To develop a method for creating spatially-controlled metabolic zonation in vitro.
  • To demonstrate the application of precise concentration gradients for inducing zonation.
  • To enhance the physiological relevance of in vitro liver models.

Main Methods:

  • Utilized a microfluidic device to establish concentration gradients.
  • Applied exogenous hormones (insulin, glucagon) and inducers (3-methylcholanthrene).

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  • Assessed metabolic zonation through periodic acid-Schiff staining (glycogen), carbamoyl phosphatase synthetase I staining (urea), and cell viability assays.

    • Main Results:

    • Successfully created spatial zonation across multiple hepatocyte metabolic functions.
    • Demonstrated gradients in carbohydrate metabolism (glycogen storage).
    • Showcased gradients in nitrogen metabolism (urea production) and drug metabolism (conjugation, degradation).

    Conclusions:

    • The developed microfluidic system enables precise control over hepatocyte metabolic zonation.
    • This advanced control is essential for creating physiologically relevant in vitro liver models.
    • The findings will advance drug metabolism and toxicology studies using in vitro constructs.