Organoid Based Screening Platform
- Increasingly recognized by global agencies (e.g., FDA, EMA, OECD) as part of New Approach Methodologies (NAMs) for safety assessment
- Enable investigation of organ-specific toxicity pathways, including oxidative stress, inflammation, and apoptosis
- Better mimic human physiology than traditional 2D cell lines or animal models, improving translational relevance
- Compatible with high-throughput formats for early-stage compound screening and dose-response profiling
Organoids
- Central to drug metabolism and detoxification, primary site of dose-limiting toxicity.
- Key Endpoints:
- Cell Viability (ATP-based luminescence)
- Liver Enzyme Release (ALT, AST)
- Oxidative Stress & Mitochondrial Function
- Morphological Imaging
- Gene Expression (CYP3A4, HMOX1, BCL2)
- First site of exposure for orally administered compounds; vital for absorption and barrier integrity.
- Key Endpoints:
- Cell Viability
- Barrier Integrity (FITC-dextran leakage, TEER)
- Inflammatory Response (IL-8, TNF-α)
- Oxidative Stress (DCFDA, MitoSOX)
- Gene Expression (LGR5, VIL1, MUC2, CLDN3)
- Critical for drug clearance and electrolyte balance; highly sensitive to toxic insults.
- Key Endpoints:
- Cell Viability
- Injury Biomarkers (NGAL, KIM-1)
- Tubular Function (Dextran-FITC or albumin uptake)
- Oxidative Stress (DCFDA, MitoSOX)
- Gene Expression (HMOX1, BCL2, SLC22A2, PAX2)