Cholestasis | InSphero

Mechanistic Assays

Cholestasis

Predict cholestasis by co-exposure of drugs with bile acids

Cholestatic and mixed hepatocellular/cholestatic injuries account for up to 50% of all cases of drug-induced liver injury (1). Drug-induced cholestasis (DIC) is caused due to interference of drugs with hepatobiliary export mechanisms. Inhibition of bile acid (BA) transport results in intrahepatic accumulation of BAs, causing induction of apoptosis (2). 3D InSight™ Human Liver Microtissues are a perfect tool to study these effects, as they establish extensive bile canaliculi and active bile acid transport through BSEP and MRP2 transporters (3).

  • Identify potentially cholestatic drugs using a primary human liver model with active hepatobiliary bile-acid transport
  • Predict cholestatic liabilities with a specificity of 100% and 86% sensitivity testing co-exposure of bile-acids and known cholestatic drugs
  • Ensure reproducibility and increase throughput with a standardized, pre-qualified 3D model in 96-well format

Example Data

Prediction of cholestatic risk based on cholestatic index. Cholestatic index values of a panel of hepatotoxicants were determined in 3D InSight™ Human Liver Microtissues after 14 days of repeated exposure, resulting in 86% specificity and 100% sensitivity. Viability was assessed by albumin secretion. Figure modified from (4).

References

  1. Björnsson et al., Hepatology, 2005
  2. Yang et al., Journal Pharm Sci, 2013
  3. Letzsch et al., GEN Engineering & Biotechnology News, 2015
  4. Hendriks et al., SciRep, 2016

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