Human stem cells derived from umbilical cord blood were introduced into the hearts of immunodeficient mutant NSG W41 mice. A few weeks after the successful transplantation, the animals were administered 17b-estradiol (E2), the most potent and prevalent form of estrogen in the body. This substance aids the survival of human stem cells, enhances the differentiation of B-lymphocytes, and boosts the production of antibodies against viruses and bacteria.
The resulting TruHuX humanized mice possess fully developed human immune systems, including lymph nodes, germinal centers, B-lymphocytes, and plasma cells. These mice also produce highly specific antibodies and autoantibodies analogous to those in humans.
TruHuX mice are capable of producing neutralizing antibodies to Salmonella Typhimurium and the SARS-CoV-2 virus after vaccination. Additionally, they can develop full-blown autoimmunity characteristic of systemic lupus erythematosus after the introduction of pristane, a terpenoid alkane that induces autoimmune diseases.
According to the scientists, TruHuX mice open new avenues for the development of immunotherapies and vaccines, as well as for modeling human diseases. Furthermore, they may reduce the need for using non-human primates in biomedical research.
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