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Thursday, October 21, 2010

Researchers Create a "Humanized" Mouse for Liver Disease Studies

Long-awaited breakthroughs in developing preclinical animal models are signaling a new era for liver-targeted viruses and beyond

By Jessica Wapner October 21, 2010
Source: Scientific American

Summary by C.D. Mazoff

The biggest reason not much progress has been made against viral diseases that attack the liver is the lack of an effective research model.  Chimpanzee research is prohibited by ethical and financial concerns, and cell cultures in the lab aren’t the same as a live model.

Scientists who have been working with mice needed a way to mimic the human immune system without destroying the innate immune response against the viruses so that they could observe how viruses and treatments against them work.

Recently researchers at the Salk Institute for Biological Studies succeeded in producing a healthy population of mice with consistently high amounts of human liver cells that are susceptible to both HBV and HCV and that are able to mimic a human response to the viruses.

The antiviral immune response, however, is not yet on par with that seen in humans, but researchers feel the ultimate goal—a single animal with both features humanized—is within reach.

Still, significant barriers remain: the liver and immune components should ideally be from the same person, but the human liver and immune cells required for transplantation are hard to come by. A possible solution would be to start with stem cells that can differentiate into liver and immune components inside the mouse, an approach that is being investigated.

The ability to create a mouse with cells from a single person would mean that eventually patients could have their very own personalized animal models for studying the potential impact of a drug. This would be a vast improvement for preclinical drug development for many pathogens, "The results...would be much more predictive of what would happen in people," says Charlie Rice who leads a research group at The Rockefeller University studying mouse models for hepatitis C.

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