Monitoring hepatotoxicity

Often the toxic impact of a drug candidate is first noted in the liver.

Randall C Willis
ABBOTT PARK, Ill.—Often the toxic impact of a drug candidate is first noted in the liver. Unfortunately, when researchers want to screen for toxicity in vitro, their efforts can be frustrated by morphological changes arising from liver cell culturing that may mask the effects of the drugs. To address this issue, researchers at Abbott Laboratories recently developed a 3D-like hepatocyte sandwich culturing technique that minimizes these effects.
 
As they described at the recent Society for Biomolecular Sciences meeting, the researchers established cultures of hepatocytes to form monolayers on collagen pads or more natural matrices when sandwiched between the collagen and Matrigel. They then used Affymetrix arrays to monitor gene expression and Molecular Devices' Discovery-1 system to monitor morphological changes when exposed to drugs.
 
The researchers found that the sandwiched cultures had a more normal in-vivo-like appearance, forming biliary canaliculi and appropriate actin fiber development, and suffered fewer gene expression changes than monolayer cultured cells. Furthermore, drugs known to negatively impact liver function showed similar effects in the sandwich culture, suggesting that the conditions more closely mimicked in vivo behavior.

Randall C Willis

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