Humanized Mouse Models

Humanized Mouse Models

Humanized mouse models are based upon cancer cells isolated from humans. Several characteristics of mice can be optimized to ensure that tumor growth will model that of a human. These models are commonly used to test out cancer therapies and drugs, as they are relatively cheap and efficient when compared to humans.

Mice used for humanized models must have several properties that enable them to successfully accept donor cells. Some mice have their immune systems artificially removed, preventing an autoimmune response to foreign cells after seeding. This allows researchers to effectively grow human cells in a murine organism, which provides a suitable environment for chemotherapy testing. Although such an environment is already better than a human patient, there are other optimizations that can make mice even better suited for in vivo testing. Mice may have a human immune system given to them by means of stem cell implantation [1], further improving the similarity of the environment to human tissues. This allows for effective tracking of drug effects in the context of human immune systems, which have significant effects on the functionality of a given drug.

Sanitary precautions are of utmost importance in dealing with humanized mice, as the lack of an immune system renders them extremely vulnerable to foreign pathogens. Careful cell implantation and controls are necessary for humanized mouse models, which can take a few weeks of monitoring to deliver results. Common mice used for such models include NSG and NOG mice, which were independently developed to impair their immune systems. As immune response systems are incredibly complex, several decades of research have gone into developing such immunodeficient mice. 

Cancer cells may be implanted in a host mouse orthotopically (occurring in the same part of the body) or subcutaneously (just below the skin). Orthotopic models are more likely to accurately simulate real human tumor growth, as the tumor will be grown in the setting of its origin (i.e a liver tumor will be implanted in the mouse’s liver). Subcutaneous implantation, though, provides better access to a tumor and can simplify quantification of a tumor’s size.

Data analysis in context of humanized mouse models is similar to that in clinical trials; tumor growth is recorded, and the effects of various therapies are compared to determine overall efficiency. After a given drug has proven its efficiency in a mouse, it may then be tested or administered to humans.

References:

[1] Walsh, Nicole C., et al. “Humanized Mouse Models of Clinical Disease.” Annual Review of Pathology: Mechanisms of Disease, vol. 12, no. 1, 2017, pp. 187–215., doi:10.1146/annurev-pathol-052016-100332.

Humanized Mouse Models provided by Altogen Labs:

CD34+ humanized mice
Humanized CD34+ mice represent an important research tool for in vivo analysis of safety and effectiveness of test articles to modulate the immune system. Humanized CD34+ mice are are commonly used in the fields of oncology, infectious disease, and graft vs host disease.

PBMC humanized mice
Humanized PBMC mice have fast engraftment rate using adult peripheral blood mononuclear cells. Humanized PBMC mouse model are useful for studying hematopoiesis, immunology, transplantation, infectious diseases, and cancer. The most common host strain is the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice.