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A microfluidically perfused three dimensional human liver model.

Knut Rennert1, Sandra Steinborn1, Marko Gröger2

  • 1Institute of Biochemistry II, Jena University Hospital, 07743 Jena, Germany.

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|September 1, 2015
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Summary
This summary is machine-generated.

Researchers developed a novel 3D liver organoid in a microfluidic biochip, integrating non-parenchymal cells (NPCs) and hepatocytes. This advanced model mimics human liver physiology for in vitro research.

Keywords:
Dynamic cell cultureLiverMicrofluidic biochipOrganoidOxygen

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Area of Science:

  • Hepatology and Regenerative Medicine
  • Biotechnology and Bioengineering
  • Cell Biology

Background:

  • Non-parenchymal cells (NPCs) are crucial for hepatocyte function and liver homeostasis.
  • Existing in vitro models often fail to replicate the complex microenvironment of the human liver sinusoid.
  • There is a need for advanced models to study human liver physiology under near-physiological conditions.

Purpose of the Study:

  • To establish a novel 3D liver organoid model that integrates NPCs and hepatocytes within a microfluidic biochip.
  • To mimic the structural and functional aspects of the human liver sinusoid, including the space of Disse and vascularization.
  • To create a tool for studying human hepatocellular physiology in vitro under perfusion.

Main Methods:

  • Development of a 3D liver organoid comprising a vascular layer (endothelial cells, macrophages) and a hepatic layer (stellate cells, hepatocytes).
  • Embedding the organoid in a microfluidic biochip with a suspended membrane mimicking the space of Disse.
  • Integration of luminescence-based sensor spots for online oxygen consumption measurement and application of microfluidic perfusion.

Main Results:

  • The microfluidic perfusion induced expression of key proteins like ZO-1, transferrin, ASGPR-1, and MRP-2 transporter.
  • Perfusion led to increased hepatobiliary secretion of 5(6)-carboxy-2',7'-dichlorofluorescein.
  • Enhanced formation of hepatocyte microvilli was observed under perfusion, indicating improved cellular function.

Conclusions:

  • The perfused liver organoid accurately replicates key morphological and functional characteristics of the human liver.
  • This model serves as a valuable new in vitro research tool for studying human hepatocellular physiology.
  • The system allows for investigations under conditions closely resembling the physiological situation in vivo.