Humanized Mice Make Better Models

Mice with miniature human livers more accurately test a drug’s toxic side effects.

Jul 13, 2011
Jef Akst

WIKIMEDIA COMMONS, POLARQUEEN

Mice with implanted 20-millimetre-long artificial human livers break down toxins in a way that is closer to how humans do it than traditional lab mice, according to a study published this week (July 11) in the Proceedings of the National Academy of Sciences. This insight can provide researchers with better models for testing  drug toxicity.

Researchers at the Massachusetts Institute of Technology grew the tiny human livers by seeding plastic scaffolds with mouse fibroblasts, human hepatocytes, and human liver endothelial cells. They then implanted the artificial organs into mice. Testing the animals with drugs known to be metabolized differently in mice and humans, the humanized mice performed much more like humans than normal mice. Despite the fact that the implants only contained about 500,000 human liver cells (whereas a full mouse liver contains tens of millions), the mice produced the same metabolites as humans do and showed the same metabolic interactions between drugs.

"The implants are still a long way from being a liver, so the human metabolism is remarkable," immunologist James Di Santo at the Pasteur Institute in Paris, who was not involved in the study, told Nature.

Previous efforts to create such humanized mice have involved injecting human cells into mice with damaged livers. As the human cells repair the damage, they take up residence the liver, but the process takes months to complete and the resulting livers contain a variable proportion of human cells. The new technique takes just a couple of weeks, making it easier for scientists to spot potential toxic side effects of drugs in animal models before moving to human trials, saving money and possibly avoiding unexpected health problems in clinical trials, the authors argue.