3D InSight™ 14 Day Hepatotoxicity Testing Service

Predict potential drug induced liver injury (DILI) in vitro using a physiologically relevant 3D human liver model

3D InSight™ 14 Day Hepatotoxicity Testing Service

  • Leverage metabolically competent 3D InSight™ Human Liver Microtissues in a standardized 14 day, repeat-dose experimental setup
  • Predict hepatotoxicity in an extensively validated 3D model system that achieves > 70% sensitivity and > 90% specificity classifying more than 100 known DILI compounds
  • Enhance data quality and predictions with highly standardized, reproducible model
  • Receive results within 3-4 weeks following receipt of compounds of interest

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Service at a Glance

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  •  Hepatotoxicity Testing Service, workflow

    Our 14 day repeat-dosing protocol

  • Hepatotoxicity Testing Service, Microtissue ExpressionOur organotypic 3D liver model. 3D InSight™ Human Liver Microtissues are composed of pooled multi-donor primary human hepatocytes (PHH) co-cultured with Kupffer cells.  They display polarized, cuboidal shaped hepatocytes, integration of CD68+ Kupffer cells, and formation of functional bile canaliculi (BSEP shown), representing intact cholestatic and inflammatory mechanisms of DILI.

  • Hepatotoxicity Testing Service, Microtissue Functionality

    Robust, stable CYP profile. 3D InSight™ Human Liver Microtissues are metabolically competent in long-term culture, as demonstrated by active turnover of CYP substrate probes. Composed of pooled hepatocytes from 5 male and 5 female donors, the model more closely approximates the average human metabolic profile.

     

  • Hepatotoxicity Testing Service- IC50 reproducibilityReproducible and sensitive. Long-lived Human Liver Microtissues enable 14 day exposure with repeat dosing, improving assay sensitivity. Our highly uniform, standardized model produces reliable IC50 data (Chlorpromazine shown) across microtissue production runs, ensuring reproducibility for longitudinal studies.

  • Hepatotoxicity Testing Service- ATP Reproducibility

    ATP assay reproducibility. 3D InSight™ Human Liver Microtissues (MT) were cultured for 14 days (untreated) and intra-tissue ATP content was assessed. In each assay (n = 40) average relative light units (RLU) from triplicates (3 MT) was set to 100%. Relative standard deviation (SD) of the mean of 40  assays is depicted. Average relative SD is 14.6%.

     

  • Assess effects of drug exposure with 14 day repeat dose protocol
  • Leverage greater mechanistic accuracy
  • Screen in a physiologically relevant model
  • Gain clinically relevant insights from a single endpoint DILI assay
  • Gold-standard cell viability assay

Catalog # SP-02-122-01
Model system 3D InSight™ Human Liver Microtissues (multi-donor hepatocytes, co-culture with Kupffer cells)
Minimum number of compounds 1  
Standard experimental setup 14 day drug exposure with cell viability endpoint at day 14  
Number of dosings 3 (Days 0, 5, and 9)  
Tested compound concentration 7-point dose-response curve  
Positive control compound Chlorpromazine  
Endpoint ATP (Promega CellTiter-Glo®)  
Data analysis



Dose-response for cell viabillity IC50ATP)  
IC50 values  
Margin of Safety (MOS) calculation if cmax values are known  
Hill-slope, minimum and maximum viability  
Written report  

Compound Characterization

Toxicity testing of compounds rated according to likelihood of causing drug-induced liver injury (DILI) in humans. Eight compounds were tested on Human Liver Microtissues using the 14 day testing protocol, then categorized by potential DILI severity according to clinical data. Cmax values were taken from human in vivo studies.

Hepatotoxicity Testing Service- Compound Characterization

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