For the first time, scientists have cross-bred mouse and human genes. Immune SystemResearchers say these human-like animals could accelerate drug development.
When faced with an infection, these “humanized” mice generate immune cells that mimic the structure and diversity of human immune cells. inflammation In the mouse body, Autoimmune disorders The researchers found a form of lupus that closely resembles that seen in humans.
The scientists described their findings in a paper published June 25 in the journal Nature. Nature Immunology.
These aren’t the first humanized mice ever bred. Laboratory animals are a staple of research because they allow researchers to study features of the human immune system in a live animal. This helps test the safety and effectiveness of new drugs and vaccines for infectious diseases before they are tested in humans.
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But researchers have struggled for years to create humanized mice that respond to infections exactly the way humans do: Previous attempts have produced approximations of the human immune system but lacked certain human characteristics, say the team that wrote the new paper. statement.
To develop a better humanized mouse, the researchers first bred mice that were genetically engineered to have weakened immune systems. When the mice were a day or two old, the team injected human stem cells into the animals’ hearts. Stem CellsExtracted and purified from umbilical cord blood, these cells had the ability to become any type of immune cell.
The animals’ hearts pumped the stem cells into bone marrow, the soft, spongy tissue in the mice’s bones, where they Immune cells are normally generatedBecause the mice were immunocompromised, the human stem cells were able to easily establish themselves in the bone marrow.
A few weeks later, the team gave the mice a dose of the human version of the sex hormone estrogen, which primarily Female Sexual and Reproductive Developmentbut it also plays a major role in forming immature stem cells. Mature specialized immune cells.
When injected with human estrogen, the mice began to produce large numbers of human immune cells, including T cells, Attacking bacteria directlyand B cells kill the bacteria. antibody It helps to label pathogens so they can be destroyed.
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 coronavirus. SARS-CoV-2Similarly, Salmonella typhi BacteriaMice infected with the bacteria that causes typhoid fever developed antibodies against the pathogen.
The new mouse model could be a valuable tool for biomedical research, the researchers said. In particular, they said the mice could be useful in vaccine development. Dr. Paolo Casaliis a professor of medicine at the University of Texas and co-senior study author.
The new mice have a “100% human immune system,” so researchers can use them to test how the vaccine works in vivo. In this early stage of research, such tests can’t be done in humans for ethical reasons, Casali told Live Science.
The mice could also be used to develop new treatments that work by fine-tuning the activity of the immune system. Cancer Checkpoint Inhibitors“These drugs help the immune system destroy cancer cells more effectively,” he said.
Using mice with human immune systems could facilitate this type of research and may even eliminate the need to use non-human primates, the team said in a statement.
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