Breakthrough in Biomedical Research: Scientists Create First Mouse with Functional Human Immune System

In a groundbreaking achievement, scientists at The University of Texas Health Science Center at San Antonio have successfully created the first mouse model with a fully functional human immune system. This innovative breakthrough has the potential to revolutionize the development of immunotherapies and vaccines, paving the way for significant advancements in biomedical research.

Why Mice are Ideal for Human Research

Mice have been a popular choice for biological and biomedical research due to their small size, ease of handling, and genetic modification capabilities. However, there has been a limitation in using mice for human research, as many mouse immune genes do not match their human equivalents, leading to inaccurate predictions of human immune responses. The creation of a “humanized” mouse model has been a high priority to overcome this challenge.

What are Humanized Mice?

The concept of humanized mice is not new, with scientists first creating them in the 1980s to study human HIV infection. These mice were made by injecting immunodeficient mice with human cells, such as peripheral lymphocytes or hematopoietic stem cells. While these models have been useful, they have limitations, including a short lifespan and incomplete immune systems.

Meet the TruHuX Mouse

The team, led by Dr. Paolo Casali, has developed a new humanized mouse model, named TruHuX (Truly Human X), by injecting immunodeficient NSG W41 mutant mice with human stem cells purified from umbilical cord blood. The mice were then hormonally conditioned with 17b-estradiol (E2), a potent form of estrogen, which helps human stem cells survive and boosts the production of B lymphocytes, essential for antibody production.

Features of the TruHuX Mouse

The TruHuX mouse possesses a fully developed human immune system, including lymph nodes, germinal centers, thymus, human epithelial cells, human T and B lymphocytes, memory B lymphocytes, plasma cells, and the ability to produce specific antibodies.

How Effective are TruHuX Mice?

These mice can mount mature antibody responses to pathogens, such as Salmonella Typhimurium and SARS-CoV-2 (COVID-19), and can even develop systemic lupus autoimmunity when injected with pristane, an oil that triggers inflammation.

Future Possibilities

This discovery opens new doors for human in vivo experimentation, including the development of immunotherapies, such as cancer checkpoint inhibitors, and the creation of human vaccines for bacterial and viral infections. The TruHuX model can also be used to model human diseases, allowing researchers to better understand diseases and develop treatments.

Estrogen’s Role in Immunity

Interestingly, this study highlights the role of estrogen in boosting the survival of human stem cells and enhancing antibody production. Dr. Casali hopes this finding will spark further research into how estrogen affects the immune system.

What’s Next?

Dr. Casali’s team is now using the TruHuX model to study the human immune response to SARS-CoV-2 at both systemic and local levels, as well as investigating the role of nuclear receptor RORα in generating memory B lymphocytes and exploring the epigenetic mechanisms behind plasma cell production.

This breakthrough not only enhances our understanding of the immune system but also holds promise for future medical advancements that could benefit humanity in unimaginable ways.

Historical Context:

The concept of humanized mice dates back to the 1980s, when scientists first created them to study human HIV infection. Since then, there have been several attempts to develop more advanced humanized mouse models, but they have been limited by their short lifespan and incomplete immune systems. This breakthrough by Dr. Paolo Casali’s team at The University of Texas Health Science Center at San Antonio marks a significant advancement in the field, as it has created a mouse model with a fully functional human immune system.

Summary in Bullet Points:

• Scientists at The University of Texas Health Science Center at San Antonio have created the first mouse model with a fully functional human immune system, named TruHuX (Truly Human X). • The TruHuX mouse was developed by injecting immunodeficient NSG W41 mutant mice with human stem cells purified from umbilical cord blood and conditioning them with 17b-estradiol (E2), a potent form of estrogen. • The mouse possesses a fully developed human immune system, including lymph nodes, germinal centers, thymus, human epithelial cells, human T and B lymphocytes, memory B lymphocytes, plasma cells, and the ability to produce specific antibodies. • The TruHuX mouse can mount mature antibody responses to pathogens, such as Salmonella Typhimurium and SARS-CoV-2 (COVID-19), and can even develop systemic lupus autoimmunity when injected with pristane. • This breakthrough has the potential to revolutionize the development of immunotherapies, such as cancer checkpoint inhibitors, and the creation of human vaccines for bacterial and viral infections. • The study highlights the role of estrogen in boosting the survival of human stem cells and enhancing antibody production, and Dr. Casali hopes this finding will spark further research into how estrogen affects the immune system. • The TruHuX model can be used to model human diseases, allowing researchers to better understand diseases and develop treatments. • The team is now using the TruHuX model to study the human immune response to SARS-CoV-2 and investigating the role of nuclear receptor RORα in generating memory B lymphocytes and exploring the epigenetic mechanisms behind plasma cell production.