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Assessment of a Micropatterned Hepatocyte Co-Culture System to Detect Compounds that Cause Drug Induced Liver Injury in Humans

Liver Injury remains a major reason for late stage drug attrition making predictive assays that can be deployed early in the drug discovery process desirable. Xu et al., 2008 have shown that drug induced liver injury can be predicted to some extent using primary human hepatocytes in sandwich cultures and high content imaging of key cell injury endpoints. The sensitivity of this assay was approximately 50% with a 0-5% false positive rate. While high content imaging using sandwich cultures represents a key advance in the field, the sensitivity of the assay needs to be further improved. One can hypothesize that the low sensitivity could be due to the fact that the assay was only performed at 24 hours and that longer incubation with compounds could improve outcomes. HepatoPac™ is used in a 96-well format to detect the drug induced liver injury potential of 45 compounds previously utilized in the Xu assay.

 

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