New research shows that it is now possible to breed mice with a fully functional human immune system. (Image credit: Evgenyi_Eg via Getty Images)
For the first time, scientists have created mice with a fully-fledged human immune system. Researchers say these human-like creatures will improve the process of drug development.
When confronted with an infection, these “humanized” mice produce immune cells that replicate the structure and diversity of cells produced by humans. When the mice are injected with a chemical that causes widespread inflammation, they develop a version of the autoimmune disease lupus similar to that seen in humans, the researchers found.
The scientists presented their findings in a paper published June 25 in the journal Nature Immunology.
These aren't the first humanized mice to be bred — lab animals play a key role in research because they allow scientists to study the human immune system in a living organism. This helps test the safety and effectiveness of new drugs and vaccines against infectious diseases before they are tested on humans.
However, for years, researchers have sought to create humanized mice that respond to infection as well as humans do. Previous attempts have produced close approximations of the human immune system, but they lacked a number of human characteristics, the team behind the new paper said in a statement.
To create a more humanized mouse, the scientists first bred mice genetically modified to have weakened immune systems. When the mice were just 1-2 days old, the team injected human stem cells into their hearts. These stem cells, extracted and purified from umbilical cord blood, were capable of developing into any type of immune cell.
The stem cells were then pumped into the soft, spongy tissue inside the mice's bones, known as bone marrow, where immune cells are normally made. Because the mice were immunocompromised, the human stem cells were able to easily take up residence in the bone marrow.
A few weeks later, the team injected the mice with a human version of the sex hormone estrogen. The hormone is best known for its role in supporting female sexual and reproductive development, but it also plays an important role in transforming immature stem cells into mature, specialized immune cells.
After being injected with human estrogen, the mice began producing a variety of human immune cells. These included T cells, which directly attack germs, and B cells, which produce antibodies that kill germs and help mark pathogens for destruction.
To see how the humanized mice would respond to the vaccine, the team injected the animals with the Pfizer-BioNTech COVID-19 vaccine. In response, the mice produced human antibodies against the SARS-CoV-2 coronavirus. Similarly, when exposed to proteins from the Salmonella typhi bacteria, which causes typhoid fever, the mice produced antibodies against the pathogen.
The new mouse model could be a valuable resource for biomedical research, the scientists said. In particular, such mice could be useful for developing vaccines, said Dr. Paolo Casali, a co-author of the study and a professor of medicine at the University of Texas.
Because the new mice have “100% human immune systems,” researchers can use them to evaluate how vaccines will work in vivo. In the early stages of research, such tests cannot be done on humans for ethical reasons, Casali told Live Science.
The mice could also be useful for developing new treatments that target immune system activity, such as cancer checkpoint inhibitors, he added. These drugs help the immune system more effectively target cancer cells to destroy them.
The group said using mice with human immune systems could make it easier to conduct such studies, potentially eliminating the need to use non-human primates.
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