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Health

A New Way to Test Drugs: in Mice With Human Livers

80beatsBy Joseph CastroJuly 13, 2011 2:15 AM

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mouseface.jpg

What’s the News: While mice are a major tool for biomedical research, they’re not always useful for testing the toxicity of pharmaceutical drugs because their livers don’t react to drugs the same way that human livers do. But in a new study, published in the journal PNAS

, scientists at MIT have gotten around this issue by implanting mice with miniature, humanized livers. Researchers may be able to use the artificial organs to help create drugs for diseases like hepatitis C

, which mice don’t normally contract, and improve the development of other drugs. "In the near term, we envision using these mice alongside existing toxicology models to help make the drug development pipeline safer and more efficient," said MIT biomedical engineer Alice Chen (via LiveScience

). How the Heck:

  • The MIT team first developed tissue scaffolds that are the same size, shape, and texture of contact lenses. In the scaffolds, the researchers combined human liver cells (hepatocytes), which quickly lose their function after being removed from the body, with other mouse and human cells for nutrients and support.

  • After the researchers implanted the scaffolds into the mice’s abdominal cavities, it took the artificial livers about a week to fully integrate into the animals. The researchers did not remove the mice’s existing livers. The scaffold gel is able to partially protect the foreign cells from the mice’s immune systems, giving researchers weeks to test drugs on the humanized livers.

  • The team tested the artificial livers by injecting the rodents with the compounds coumarin and debrisoquine, which mice and humans break down differently. The mice produced the same metabolites—breakdown products—that humans do.

What’s the Context:

  • Scientists created “chimeric” livers last year by repairing damaged livers in mice with human liver cells. An issue with this method is that it takes months for the chimeric livers to form.

  • Additionally, this technique requires that the mice have weakened immune systems, so that their bodies don’t immediately reject the human cells; this limits the use of the chimeric livers in studying certain diseases, according to an article from MIT.

The Future Holds: The researchers are now studying how the artificial livers respond to other drugs whose human metabolites are known. They are also working on developing humanized livers that are even smaller. (via Nature

)

Image: Wikimedia Commons/Rama

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