Mice have long been used as a model system for studying the human immune system, from which many basic principles of immunology have been uncovered. As discoveries made using mouse models show promise for therapeutic development for human patients, human-mouse models can serve as an ideal model of the human immune system prior to clinical trials.
Iterations of the Human-Mouse Model
The first version of the human-mouse model system was the SCID-hu-PBL model described by Mosier, et al. in 1988 in Nature, where human peripheral blood leukocytes were injected intravenously into mice with severe combined immunodeficiency to reconstitute a functional human immune system inside the mouse. Scientists working on the SCID-hu-PBL mice showed that the PBL persisted in the mice through the detection of human T cells and B cells in the mouse blood, though the human cells were eventually eliminated by the mouse’s innate immune system.
The non-obese diabetic mouse strain (NOD), which predated the SCID-hu-PBL strain, was first described by Makino, et al. in 1980. NOD mice are known to have deficiencies in NK cells and myeloid cells. Researchers combined NOD and SCID mice, described by Greiner, et al. in 1995, to form a new strain that showed improved engraftment rates of human cells.
A further improvement over the NOD-SCID mice came when researchers (Ito, et al. 2002) knocked out the common gamma chain of cytokine receptors, leading to a new strain of NOD-SCID-Gamma mice, also known as NSG mice. When the gamma chain (which is shared by receptors for IL-2, IL-4, IL-7, and other cytokines) is deleted, the functions of all associated cytokines are eliminated. The development of this mouse strain further increased the efficiency of transferring human cells into mice.
Using Human-Mouse Models in Your Lab
Our PBMC have been successfully used to create human immune systems within immune deficient mice. Customers have used this model to evaluate cytokine release syndrome observed in immuno-oncology therapies. As more advanced mouse models are created to include human HLA molecules and human cytokine secretion, experiments utilizing neo-antigen or autoantigen specific T cells could be explored.
Looking for more? Explore these two abstracts from AACR 2019 that utilized PBMC humanized mice:
- An in vivo method for determining cancer immunotherapy induced cytokine release syndrome utilizing PBMC humanized mice
- Increased sensitivity for detecting cytokine release syndrome with cancer immunotherapy using a PBMC humanized NSG-SGM3 mouse model