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Reconstituting Cytoarchitecture and Function of Human Epithelial Tissues on an Open-Top Organ-Chip
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Tissue-on-a-Chip: Microphysiometry With Human 3D Models on Transwell Inserts.

Christian Schmidt1, Jan Markus2, Helena Kandarova3,4

  • 1cellasys GmbH, Kronburg, Germany.

Frontiers in Bioengineering and Biotechnology
|August 28, 2020
PubMed
Summary
This summary is machine-generated.

This study introduces a novel multichannel intestine-on-a-chip system for monitoring transepithelial electrical resistance (TEER) in 3D intestinal models. The automated assay effectively detects barrier disruption by chemicals, offering a promising tool for in vitro diagnostics.

Keywords:
automated air–liquid interfaceintestinal modellabel-free monitoringmicrophysiometrytransepithelial electrical resistance

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Area of Science:

  • Biotechnology
  • In vitro toxicology
  • Tissue engineering

Background:

  • Microphysiometry is established for monitoring cell metabolism and interactions, primarily in 2D cell cultures.
  • Previous work demonstrated monitoring of 3D skin constructs using air-liquid interface (ALI) and 3D-printed encapsulation.
  • There is a need for advanced in vitro models to assess drug absorption and toxicity in complex 3D tissues.

Purpose of the Study:

  • To develop and validate an optimized multichannel intestine-on-a-chip system.
  • To enable real-time, time-resolved monitoring of transepithelial electrical resistance (TEER) in a 3D small intestinal tissue model.
  • To demonstrate the system's capability in detecting chemical-induced barrier disruption.

Main Methods:

  • Utilized a commercially available 3D small intestinal tissue model (EpiIntestinal™).
  • Implemented an automated multichannel assay maintaining an air-liquid interface (ALI) for 1 day.
  • Periodically applied measurement medium or test substances within a 60-minute cycle, including a cytotoxic benchmark chemical (sodium dodecyl sulfate).

Main Results:

  • Successfully monitored TEER in the 3D intestine model using the multichannel intestine-on-a-chip system.
  • Observed a time-dependent reduction in TEER upon application of sodium dodecyl sulfate, indicating barrier disruption.
  • The automated ALI system provided time-resolved data not typically captured by standard cytotoxicity assays.

Conclusions:

  • The developed multichannel intestine-on-a-chip system is a proof-of-principle for automated, time-resolved TEER monitoring of 3D intestinal models.
  • This technology, combined with reconstructed human tissues, shows promise for in vitro toxicology, cellular metabolism, and drug absorption research.
  • The system offers a valuable tool for advanced in vitro diagnostics and research applications.