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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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Microphysiological Systems to Assess Nonclinical Toxicity

Kirk P Van Ness1, Shih-Yu Chang2, Elijah J Weber1

  • 1Department of Pharmaceutics, University of Washington, Seattle, Washington.

Current Protocols in Toxicology
|August 5, 2017
PubMed

Insights

This study introduces a novel microphysiological system (MPS) platform for improved drug toxicity testing. The renal and hepatic MPS platform better maintains cell function for more accurate toxicology investigations.

Area of Science:

  • Toxicology
  • Drug Development
  • In Vitro Models

Background:

  • Liver and kidney are primary drug toxicity targets.
  • Traditional 2-D cell cultures lack essential metabolic and transport functions.
  • This limits their use in nonclinical toxicology.

Purpose of the Study:

  • To develop a renal and hepatic microphysiological system (MPS) platform.
  • To improve in vitro models for drug toxicity assessment.
  • To better recapitulate human kidney and liver functions.

Main Methods:

  • Utilized a commercially available MPS device.
  • Developed protocols for isolating and culturing human proximal tubule epithelial cells.
  • Established methods for culturing hepatocytes and connecting renal and liver MPS.

Main Results:

  • Successfully cultured human proximal tubule epithelial cells in a renal MPS.
  • Established two methods for hepatocyte culture within an MPS.
  • Demonstrated the ability to connect renal and hepatic MPS modules.

Conclusions:

  • The developed MPS platform enhances the maintenance of critical cell functions.
  • This system offers a more predictive model for drug-induced liver and kidney toxicity.
  • The platform advances in vitro toxicology for drug development.
Keywords:
hepatocytein vitro modelsmicrophysiological systemsproximal tubule

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