Although the human tumor transplantation model relying on immunodeficient mice has been widely used in tumor immunology and the development of novel therapies, the lack of a human immune system and tumor immune microenvironment significantly restricts translational research into immune mechanisms and immunotherapies.
Immuno-humanized mouse models are established by engrafting human hematopoietic cells, lymphocytes, or tissues into immunodeficient mice, thereby reconstituting a human immune system and recapitulating human immune characteristics. These models are of great significance for studying human diseases and developing novel therapeutics.
The most common types are the Hu-PBMC mouse and the Hu-HSC mouse.
The Hu-HSC mouse model is generated by subjecting 3–4 week old NMG immunodeficient mice to sublethal irradiation, followed by injection of fresh human CD34+ HSCs via the tail vein or intrabone marrow route.
The advantage of this model is that the Hu-HSCs can differentiate into various immune cell types, including T cells, B cells, NK cells, MDSCs, and other lineage-negative cells. Furthermore, these cells are immunotolerant to the mouse host and typically do not cause GvHD. The model exhibits a long stable period and shows great potential for application in tumor immunotherapy research.
The advantage of this model is that the Hu-HSCs can differentiate into various immune cell types, including T cells, B cells, NK cells, MDSCs, and other lineage-negative cells. Furthermore, these cells are immunotolerant to the mouse host and typically do not cause GvHD. The model exhibits a long stable period and shows great potential for application in tumor immunotherapy research.
Phenotypic analysis
Fig1. Flow analysis of peripheral blood lymphocyte subpopulations in the Hu-HSC model. Human HSC (1.5E5) was injected intravenously into M-NSG mice (female and male n=10). Blood was taken at different time points after implantation ofs humanHSCs for flow cytometric analysis.
Fig2. Donor selection of the Hu-HSC model. Human HSC (1.5E5) was injected intravenously into M-NSG mice (female and male n=10). Blood was taken at different time points after implantation ofs humanHSCs for flow cytometric analysis.
Case Studies on Efficacy Evaluation
Fig. In vivo efficacy studies using the human breast cancer (MDA-MB-231) Hu-HSC model.
