Can 'humanized' mice improve drug development in the 21st century?

Chimeric mice, which have human hepatocytes engrafted in their liver, have been used to study human drug metabolism and pharmacodynamic responses for nearly 20 years. However, there are very few examples where their use has prospectively impacted the development of a candidate medication. Here, three different chimeric mouse models and their utility for pharmacology studies are evaluated. Several recent studies indicate that using these chimeric mouse models could help to overcome traditional (predicting human-specific metabolites and toxicities) and 21st century problems (strategies for personalized medicine and selection of optimal combination therapies) in drug development. These examples suggest that there are many opportunities in which the use of chimeric mice could significantly improve the quality of preclinical drug assessment.