Method Profile

MASH Donor Liver Organoids for Fatty-Acid and Acetaminophen Injury Comparisons

Donor background and fatty-acid stress are compared in multicellular liver organoids before and after acetaminophen exposure.

LiverOrganoids
White medicine container labeled Tylenol and acetaminophen.
Acetaminophen medicine container. (Austin Kirk (Au Kirk), CC BY 2.0)

Research Applications

Investigation of disease-background susceptibility and connected redox, mitochondrial and cell-injury responses.

Model & Design

iPSC-derived liver organoids containing hepatocyte-like, biliary, stellate, endothelial and Kupffer-like populations; two control and two MASH donor lines.

Experimental Format

Air–liquid-interface tissue generation; oleic-acid challenge and acetaminophen response assessed with imaging, expression and functional assays.

Model Components

  • Component

    Tissue and exposures

    Description

    Control/MASH donor-derived organoids; oleic acid at 100 μM and acetaminophen dose comparisons at 5, 25 and 50 mmol/L.

  • Component

    Measurements

    Description

    Lipid imaging/lipidomics, redox probes, mitochondrial potential, ATP and apoptosis-associated staining.

Measurements & Endpoints

  • Lipid accumulation and lipid classes
  • Inflammatory/fibrotic markers
  • Glutathione-associated and reactive-oxygen signals
  • Mitochondrial potential and ATP
  • Apoptotic staining

Analysis

Keep donor-background, fatty-acid and drug comparisons explicit. Lipidomics uses one line per group across three differentiations and is distinct from the broader model-characterization panel.

Published Evidence

  • Study Design

    Compare control and MASH cultures with and without fatty-acid pretreatment and subsequent acetaminophen challenge.

    Study Sample

    Four donor-derived cell lines for generation; lipidomics uses one control and one MASH line in three independent differentiations.

    Comparison

    Matched untreated/vehicle and fatty-acid/drug conditions; published biopsy lipid data provide an external contextual comparison.

    Finding

    MASH-background and fatty-acid-pretreated cultures showed stronger selected oxidative, antioxidant and injury changes after acetaminophen.

    Interpretation & Limits
    • Experimental millimolar acetaminophen exposures are laboratory injury conditions.
    • The donor panel and lipidomics panel are small and differ in composition.
    • The study does not establish a specific epigenetic mechanism or broad clinical drug-prediction accuracy.

Sources

  1. MASH Background Confers Enhanced Disease Susceptibility and Acetaminophen Toxicity in iPSC‐Derived Liver Organoids. Advanced Science (2026). ↗