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Artificial Human Liver Tests New Drugs

Tracy Staedter, Discovery News

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Looks Like a Panel, Acts Like a Liver

Living cells are organized on the plates using a technique called micro-patterning. Nearly 300 liver cells are placed onto 37 islands of proteins and then seeded with other cells called fibroblasts, which give rise to connective tissue. One plate has 24 groupings of the islands, for a total of about 10,000 cells.

Although the plate doesn't look like a liver, it behaves like one. The cells secrete the blood protein albumin, for example, synthesize urea, and produce enzymes that break down drugs and toxins.

Because the cells live for several weeks, the scientists were able to conduct tests using drugs known to be toxic to livers. In one test, the team showed that troglitazone, an anti-diabetic and anti-inflammatory drug removed from the market in 2000 by the FDA, had much higher toxicity levels than two other drugs approved for the same purpose.

"If you can weed out the toxic drugs early on in the process that would really be helpful," said Jennifer Elisseeff, associate professor of biomedical engineering and orthopedic surgery at Johns Hopkins University in Baltimore, Md.

The challenge, she said, is proving to pharmaceutical companies and regulatory agencies that an artificial liver model can predict toxicity just as well or better than a similar animal model.

Khetani's long-term goal is to improve the model so that the cells will live much longer. In the meantime, a startup company called Hepregen has licensed the technique and is working to introduce it into the pharmaceutical marketplace.

Related Links:

Tracy Staedter's blog: What the Tech?

Harvard-MIT Division of Health Sciences and Technology.

FDA: Drug-Induced Liver Toxicity

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Artificial Human Liver Tests New Drugs

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