Mouse Model with Human Immune System
For the first time, researchers have successfully engineered a mouse with a completely functional human immune system and a human-like gut microbiome. Consequently, this groundbreaking ‘humanized‘ mouse model eliminates much of the uncertainty in medical research and, furthermore, has the potential to revolutionize drug testing and the understanding of disease mechanisms.
Achievement in Genetic Engineering
Scientists at The University of Texas Health Science Center at San Antonio have achieved what many others have attempted and failed: creating a mouse with an immune response identical to that of humans. While mice are commonly used in research and are among the best animals for such work, they are far from perfect human analogs. A significant challenge lies in the genetic differences between mice and humans, which result in different immune responses.
This new mouse model, known as TruHuX (Truly Human) or THX, promises to overcome these barriers. Consequently, with a fully functional human immune system, the mouse’s response to treatments mirrors that of humans.
THX mice provide a platform for human immune system studies, the development of human vaccines, and the testing of therapeutics, said Dr. Paolo Casali, who, as a result, led this pioneering study.
Implications for Drug Development
For those outside the medical research field, this advancement means the potential for faster drug and immunotherapy development. It can reduce the ‘trial and error‘ period and enable scientists to enter human trials with greater confidence in the treatments’ efficacy and safety. Dr. Casali also believes that THX mice could eliminate the need for immunological and microbiological testing on non-human primates.
As a result, these mice open new possibilities for cancer immunotherapy, vaccine development against bacteria and viruses, and disease modeling.
Challenges and Future Perspectives
Although future technology may eventually create complex artificial models to replace animals in medical testing, animal models remain essential for drug development and disease research for now. Scientists have been working on perfecting humanized mouse models for decades.
The first such model, developed in the 1980s to study human HIV infection and immune response, continues to play a vital role in research. Previously, scientists created these models by injecting immunodeficient mice with human peripheral lymphocytes, immature hematopoietic stem cells, or other human cells. However, these mice often have short lifespans, suffer various health issues due to ‘humanization,’ and their immune responses differ significantly from humans.
Dr. Casali’s team began with immunodeficient mice (NSG W41 mutants), injecting human stem cells purified from umbilical cord blood into the mice’s left ventricles.
After the graft settled for several weeks, the team hormonally conditioned the mice with 17b-estradiol (E2). They previously found that this potent form of estrogen enhances stem-cell survival and lymphocyte differentiation and activates antibodies in response to viruses and bacteria.
Ultimately, THX mice are ‘super-humanized‘ with a complete human immune system – including lymph nodes, germinal centers, thymus human epithelial cells, human T and B lymphocytes. Consequently, they are capable of mounting an immune response identical to that of humans.
The team is now using THX mice to better understand the human immune response to SARS-CoV-2 and investigate the epigenetic factors involved in human plasma cell activity and antibody responses, which could lead to new viral and cancer therapies
Read the original article on: New Atlas
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