Humanized mice — engrafted with human tissues, cells, and/or genes — are a model for studying preclinical aspects of human ailments. These models help evaluate the role of genes during the development of a particular infection and how various pathological events are exhibited at the cellular level.

Over the last 20 years, the growing role of humanized model applications in biomedical research has enhanced discernment of human physiology, infection pathology, and host immunology at molecular, cellular, and organ system levels. The primary goal of biomedical research is to vanquish human infectious agents and diseases, which has been facilitated with the application of humanized mouse models.

The humanized mouse has the greater reproductive capability, translational potential, and repeatability of data compared to other primates, including conventional mice. These humanized mice are economical and safe concerning ethical concerns. The development of translational medicine has rapidly improved with the use of humanized mice.

 

 

Distinct Humanized Mice Are Used in Different Research Areas

1. Hu-PBMC for GvHD research, such as HIV/AID, etc

For in vivo study of human immunological events during a specific disease or novel vaccine development, an immune-deficient xenogeneic-GvHD based mouse model injected with human peripheral blood mononuclear cells (PBMC; “Hu-PBMC mice”) is a substantial tool. The human cell engraftment improvised with the use of humanized mice with deleted interleukin-2 (IL-2RY: NOD-SCID IL-2RY or BALB/c-Rag2 IL-2RY) (Ali et al., 2012). For the study of pathological events and therapeutic trials in HIV infection, the NRG-hu HSC mouse model (reconstituted with human HSC) is appropriate.

2. Hu-HSC (Hu-CD34) for tumor research, adoptive cell transfer, etc.

For oncological studies, humanized mice with CD 34+ cells are ideal because they have stable engraft of hematopoietic stem cells (HSC), and they are named as a huCD34+-HSC mouse. They persistently produce human cell lineage for up to 9 months.

3. Hu-NOG for the study of liver, human hematopoietic, and immune system research.

Immunodeficient mice exhibit hematopoietic cells multilineage of humans, which have cell reconstitution ability, and can be engrafted with liver, skin, pancreas, blood cancer, and tumorous mass. Humanized NOG mouse is one of these immunodeficient mice and is best for hematopoietic, immunological, and tissue grafting studies. 

 

How Are Humanized Mice Made?

1. Hu-PBMC

The peripheral blood mononuclear cells of humans are injected in immune-deficient mice intraperitoneal or intravenously. The human tumorous mass engrafted or HIV-infected cells are injected for evaluation.

2. Hu-HSC

Immune-deficient mice undergo irradiation followed by engraftment of human cells (CD34+) intravenously.  After 12 to 14 hours, humanized mice having CD45+ cells (T and B-lymphocytes) are ready for implantation of tumor cells PDX or CDX.

3. Hu-NOG

An immunodeficient mouse model was produced through radiation and engrafted with hematopoietic cell lineage of human, liver tissue, or any other tissue of concern.

 

The Importance of Humanized Mice

Cyagen humanized mice are important tools for biological research, including regenerative, immunogenic, and translational medicine. In the last decade, there have been significant accomplishments in the application of humanized mice in vaccine development for human ailments such as  Epstein-Barr Virus (EBV), Flavivirus, HIV-1, CE-antigen, and coronavirus (SARS-CoV).

A significant number of novel vaccine development experiments are ongoing in humanized mice that involve the reconstitution of immune cells. Cyagen’s humanized mice are optimal for immunodynamic and immunomodulatory studies, the study of pathological and oncological events, pharmacodynamic trials, and prediction of clinical responsiveness of a pathogen.