Innovations, challenges, and minimal information for standardization of humanized mice

Abstract

Mice xenotransplanted with human cells and/or expressing human gene products (also known as "humanized mice") recapitulate the human evolutionary specialization and diversity of genotypic and phenotypic traits. These models can provide a relevant in vivo context for understanding of human-specific physiology and pathologies. Humanized mice have advanced toward mainstream preclinical models and are now at the forefront of biomedical research. Here, we considered innovations and challenges regarding the reconstitution of human immunity and human tissues, modeling of human infections and cancer, and the use of humanized mice for testing drugs or regenerative therapy products. As the number of publications exploring different facets of humanized mouse models has steadily increased in past years, it is becoming evident that standardized reporting is needed in the field. Therefore, an international community-driven resource called "Minimal Information for Standardization of Humanized Mice" (MISHUM) has been created for the purpose of enhancing rigor and reproducibility of studies in the field. Within MISHUM, we propose comprehensive guidelines for reporting critical information generated using humanized mice.

Keywords: PDX; humanized mice; immuno-oncology; infections; regenerative medicine.

Figure 1. Development and applications of humanized mouse models

Schematic representation of the human materials (in blue), immunodeficient mouse strain characteristics and handling (black), and analyses performed (red) for different types of humanized mouse models: (A) human immunity; (B) human metabolism; (C) human infections; (D) human malignancies; (E) human immuno‐oncology. Abbreviated items are spelled out in the glossary.