Human induced pluripotent stem cell–derived liver-on-a-chip for studying drug metabolism: the challenge of the cytochrome P450 family

Isabel Tamargo-Rubio, Anna Bella Simpson, Joanne A. Hoogerland, Jingyuan Fu*

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

2 Citations (Scopus)
13 Downloads (Pure)

Abstract

The liver is the primary organ responsible for the detoxification and metabolism of drugs. To date, a lack of preclinical models that accurately emulate drug metabolism by the human liver presents a significant challenge in the drug development pipeline, particularly for predicting drug efficacy and toxicity. In recent years, emerging microfluidic-based organ-on-a-chip (OoC) technologies, combined with human induced pluripotent stem cell (hiPSC) technology, present a promising avenue for the complete recapitulation of human organ biology in a patient-specific manner. However, hiPSC-derived organoids and liver-on-a-chip models have so far failed to sufficiently express cytochrome P450 monooxygenase (CYP450) enzymes, the key enzymes involved in first-pass metabolism, which limits the effectiveness and translatability of these models in drug metabolism studies. This review explores the potential of innovative organoid and OoC technologies for studying drug metabolism and discusses their existing drawbacks, such as low expression of CYP450 genes. Finally, we postulate potential approaches for enhancing CYP450 expression in the hope of paving the way toward developing novel, fully representative liver drug-metabolism models.

Original languageEnglish
Article number1223108
Number of pages9
JournalFrontiers in Pharmacology
Volume14
DOIs
Publication statusPublished - 28-Jun-2023

Keywords

  • CYP450
  • drug metabolism
  • hiPSC
  • OoC
  • Organoids

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