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MIT: 'Micro' livers could aid drug screening
Date:11/18/2007

hich has over 500 different functions, they also evaluated its gene expression profiles, measures of the levels of gene activation in the tissues. They found that these profiles are very similar to those of fresh liver cells, giving us confidence that other [liver] functions are preserved, said Khetani.

For drug testing purposes, this affinity to the human liver allows each colony to provide a window into the human livers response to a drug without having to expose human patients to the drug in a clinical trial, said Bhatia.

Further, because the engineered tissue lives for so long, it has the potential to make new types of toxicity tests possible. For instance, it opens the door to testing the effects of long-term drug use akin to taking one pill a day over multiple weeks. It also will allow more extensive testing of drug-drug interactions.

In addition to being a good biological model, the engineered tissue is designed to be seamlessly integrated into an industrial pharmaceutical science setting.

To mass-produce plates of the miniature liver models, Khetani relies on a technique called soft lithography. This technique fashions a reusable micropatterned rubber stencil from a silicon master. Each stencil contains an array of 24 wells, and each well contains a matrix of 37 tiny holes. Khetani peels and sticks the stencil onto plates and places the liver cells into the holes, patterning over 888 miniature model livers across the microwells in a matter of minutes.

In tests of drugs with a range of well-known toxicity levels, assays (chemical detection tests) on the miniature liver models showed the expected levels of toxicity. Our platform was able to predict the relative toxicity of these drugs as seen in the clinic, said Khetani. For instance, troglitazone, a drug withdrawn from the market by the FDA due to liver toxicity, showed toxicity levels much higher than its FDA-approved analogues, Rosiglitazone and Pioglitazone.<
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Contact: Elizabeth Thomson
thomson@mit.edu
617-258-5402
Massachusetts Institute of Technology
Source:Eurekalert

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