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Related Concept Videos

Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...

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Related Experiment Video

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A Flow Adhesion Assay to Study Leucocyte Recruitment to Human Hepatic Sinusoidal Endothelium Under Conditions of Shear Stress
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Fluid shear stress modulation of hepatocyte-like cell function.

Hassan Rashidi1, Sharmin Alhaque1, Dagmara Szkolnicka1

  • 1MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, EH16 4UU, UK.

Archives of Toxicology
|March 17, 2016
PubMed
Summary

Fluid shear stress enhances hepatocyte-like cell (HLC) function and phenotype. This study shows shear stress significantly improves drug metabolism and reduces fetal markers, highlighting its importance for cell-based models.

Keywords:
Albumin secretionAlpha-fetoprotein secretionCytochrome P450 MetabolismEmbryonic stem cellFluid shear stressHepatocyte-like cell

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Area of Science:

  • Hepatology
  • Stem Cell Biology
  • Biotechnology

Background:

  • Primary human hepatocytes are ideal but scarce and lose phenotype.
  • Human pluripotent stem cells offer a renewable source for hepatocyte-like cells (HLCs).
  • HLCs often exhibit unstable phenotypes and limited functionality in vitro.

Purpose of the Study:

  • To investigate the impact of fluid shear stress on HLC function and phenotype.
  • To assess improvements in drug metabolism and protein secretion under shear stress.
  • To determine if physiologic cues can enhance HLC performance for in vitro applications.

Main Methods:

  • Hepatocyte-like cells (HLCs) were cultured under static conditions and exposed to fluid shear stress.
  • Cytochrome P450 (CYP) enzyme activity (Cyp1A2, Cyp2D6) was measured.
  • Serum protein secretion, including alpha-fetoprotein, was analyzed.

Main Results:

  • Fluid shear stress increased Cyp1A2 activity approximately fivefold.
  • Sensitivity to a Cyp2D6-metabolized drug increased approximately ninefold.
  • Secretion of alpha-fetoprotein, a fetal marker, was reduced approximately fourfold.

Conclusions:

  • Fluid shear stress significantly enhances key hepatocyte functions, including drug metabolism.
  • Physiologic cues like shear stress are crucial for improving the phenotype and function of HLCs.
  • This approach holds promise for developing more robust and physiologically relevant cell-based models for drug discovery and toxicology.