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3D Cultivation Techniques for Primary Human Hepatocytes.

Anastasia Bachmann1, Matthias Moll2, Eric Gottwald3

  • 1BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany. anastasia.bachmann@gmail.com.

Microarrays (Basel, Switzerland)
|September 8, 2016
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Summary

Predicting drug toxicity requires better in vitro models. This study reviews 3D microfluidic devices for hepatocyte culture, highlighting challenges like high cell numbers and cost, suggesting simplification for broader adoption in drug development.

Keywords:
drug-induced hepatotoxicityhydrogelsin vitro modellong-term cultureprimary human hepatocytesscaffoldsthree-dimensional (3D) cell culturetwo-dimensional (2D) cell culture

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Area of Science:

  • Hepatocyte biology
  • Drug development
  • Microfluidics

Background:

  • Standard monolayer cultures of primary human hepatocytes lead to loss of function, impacting drug toxicity prediction.
  • Three-dimensional (3D) culture systems, particularly those using collagen or hydrogels, can better maintain hepatocyte morphology and liver-specific functions.
  • Perfusion techniques combined with 3D cultivation aim to further enhance and preserve hepatic functions.

Purpose of the Study:

  • To review and discuss the advantages and disadvantages of various 3D microfluidic devices for hepatocyte culture.
  • To identify key limitations hindering the widespread adoption of current 3D microfluidic systems in research and the pharmaceutical industry.
  • To propose improvements for developing more user-friendly and high-throughput devices.

Main Methods:

  • Review of existing literature on 3D microfluidic devices for hepatocyte cultivation.
  • Analysis of the benefits and drawbacks of different 3D cultivation strategies, including perfusion.
  • Evaluation of device characteristics such as cell number requirements, throughput, and equipment costs.

Main Results:

  • Current 3D microfluidic devices often require large numbers of primary human hepatocytes.
  • Low throughput and expensive equipment are significant barriers to the use of these advanced systems.
  • Existing devices are generally unattractive for routine research and drug development applications.

Conclusions:

  • Simplification of 3D microfluidic devices is crucial for increasing their acceptance.
  • Compatibility with high-throughput screening is essential for practical application in drug development.
  • User-friendly, cost-effective, and high-throughput 3D microfluidic systems are needed to improve in vitro toxicity prediction.