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A Human Reaction

Mice with modified livers respond to drugs more like people

Although mice are often used for biomedical research, they are not always helpful for pharmaceutical testing. When a drug enters the body, it passes first through the liver, where it can have potentially toxic side effects. But mouse livers don’t react to drugs the way human livers do, so a drug that harms the liver could make it all the way to human clinical trials before researchers discover the risks.

Serial Inventor Alice A. Chen, PhD ’11, winner of the 2011 Lemelson-MIT Student Prize, has also cofounded Sienna Labs with Todd Harris, PhD ’08. The biotechnology company has developed a new class of medical pigments to improve the safety and efficacy of microsurgeries for treatment of skin diseases.

Now Alice Chen, who in March earned her PhD in the Harvard-MIT Division of Health Sciences and Technology (HST), has developed a way to overcome that problem. By growing human liver tissue in mice, she can create a “humanized” mouse liver that responds to drugs the same way a real human liver does. The humanized organs could also be used to study the liver’s response to diseases such as malaria and hepatitis C.

“What’s exciting to researchers is this idea that if we can batch-create these mice with human livers, we can basically create a slew of humanlike patients to do drug development screens, or to infect with these human-specific diseases so we can develop new therapies,” says Chen, who worked in the lab of Sangeeta Bhatia, SM ‘93, PhD ‘97, professor of HST and electrical engineering and computer science.

One obstacle to creating mice with human livers is that human liver cells tend to rapidly lose their function after being removed from the body. Chen and Bhatia’s answer is a tissue scaffold that includes nutrients and supportive cells, which preserve the liver cells. The scaffold, which is the size, shape, and texture of a contact lens, can be implanted in the mouse abdomen.

In March, Chen won the $30,000 Lemelson-­MIT Student Prize for this and other work, and she also won the 2010 Collegiate Inventors Competition in the graduate-­student category. “We can all invent,” she says. “Our next challenge and responsibility is to connect our inventions to something with real-world impact.”

Chen and her colleagues are now studying how the humanized livers respond to specific drugs whose breakdown products (metabolites) are already known. That will pave the way for exploring the effects of untested drugs. “The idea that you could take a humanized mouse and identify these metabolites before going to clinical trials is potentially very valuable,” she says.

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