Liver Cell 'Library' Could Make Drug Testing Safer

by Brendon Nafziger, DOTmed News Associate Editor | October 28, 2009
Understanding the liver
is essential to drug delivery
In a medical first, scientists have created viable liver cells from adult stem cells, a breakthrough that could one day lead to the building of a liver cell "library," which would allow researchers to test how individuals from different populations respond to drugs.

If successful, this could mean scientists would be better able to predict how a person would metabolize drugs in their liver, by testing the drugs on genetically similar liver cells.

"A library could identify these potential differences in metabolism at an early stage, thus reducing late-point drug attrition rates, saving money and also potentially identifying adverse drug reaction in certain populations," Gareth Sullivan, of the University of Edinburgh's MRC Centre for Regenerative Medicine, where much of the research took place, tells DOTmed News.

In the study, out in a recent issue of the journal Hepatology, scientists at Edinburgh, along with colleagues at Harvard Medical School, created fresh liver cells by turning adult skin cells into viable stem cells. This was done by introducing a retrovirus that "convinces" the skin cells that they're really stem cells, enabling them to be transformed into liver cells or other cell types, according to Sullivan.

Currently, to test how the liver metabolizes drugs, scientists make do with primary human hepatocytes (PHHs), liver cells from cadavers or live donors.

But PHHs have huge drawbacks, according to Sullivan. Because cells removed from a liver lose activity quickly and only last around five days, PHHs are expensive. They're also generally pooled from multiple sources, an act that obliterates known distinctions in drug metabolism among populations, Sullivan says.

Currently, he and his team have created five different lines, which were drawn from Caucasians and Native Americans.

The reason for focusing on different ethnic groups is that ethnic groups, and even populations within groups, have subtly different polymorphisms, or variations in their genes, that affect how people will metabolize, or respond to medication.

The classic example of this is the response to warfarin, an anti-clotting drug. "Different people have to be prescribed different levels of warfarin, based on polymorphisms," Sullivan says. Some people, it is believed, have a genetic risk that requires them to receive lower doses of warfarin to prevent bleeding.

But research in the field could be a slog, and not just for technical reasons. The United Kingdom, where much of the research is happening, imposes tight restrictions on acquiring relevant medical samples, Sullivan says.

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