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Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip.

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  • 1Key Laboratory of Microgravity (National Microgravity Laboratory), Center of Biomechanics and Bioengineering, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. mlong@imech.ac.cn and School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.

Lab on a Chip
|January 24, 2017
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Summary
This summary is machine-generated.

Researchers developed a novel in vitro liver sinusoid chip using four primary hepatic cell types. This model replicates liver structures and functions, offering new insights into cellular interactions and immune responses under physiological conditions.

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Area of Science:

  • Hepatology
  • Biomedical Engineering
  • Microfluidics

Background:

  • Liver sinusoids involve complex interactions between four primary cell types: liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and hepatocytes.
  • Mimicking the in vivo liver sinusoid's intricate cellular interactions, spatiotemporal organization, and mechanical microenvironment in vitro is challenging.

Purpose of the Study:

  • To develop an advanced in vitro liver sinusoid chip that accurately replicates key structural and functional aspects of the native liver.
  • To investigate the impact of shear flow and multi-cellular co-culture on hepatic functions and immune responses.

Main Methods:

  • Integration of four primary murine hepatic cell types into a microfluidic chip with two adjacent channels separated by a porous membrane.
  • Quantitative analysis of flow fields using computational fluid dynamics simulations and particle tracking.
  • Assessment of albumin secretion, HGF production, CYP450 metabolism, and neutrophil recruitment under various conditions.

Main Results:

  • The liver chip successfully replicated liver-specific fenestration and cellular morphology.
  • Co-culture and shear flow synergistically enhanced albumin secretion, while shear flow alone boosted HGF production and CYP450 metabolism.
  • The model demonstrated neutrophil recruitment under lipopolysaccharide stimulation, indicating a functional immune response.

Conclusions:

  • The developed 3D in vitro liver chip effectively integrates shear flow and four primary hepatic cell types.
  • This model provides a robust platform for studying short-term hepatic cellular interactions and immune responses in a physiologically relevant microenvironment.
  • The chip advances in vitro liver modeling for research into hepatic physiology and disease.