To study the immune system in human health and disease, scientists often use genetic manipulation of mouse hematopoietic stem cells and progenitors (HSPC) as a powerful model of the system. These studies have been extremely valuable in the fight against various human diseases. However, current procedures are complex, time consuming, and expensive.
In a new study published in Communications on Nature, researchers at the University of Tsukuba have developed a new technique that can overcome the limitations associated with these models, known as bone marrow (BM) chimeric mice. This system allows scientists to observe and investigate how genetic alterations affect the phenotypes and behaviors of immune cells in a physiological environment.
The first step in generating chimeric BM mice is to use irradiation to destroy the immune system of the host mouse. BM is then acquired from a donor mouse and HSPC is isolated by a process called fluorescence-activated cell classification (FACS). HSPCs are then genetically engineered and then incorporated into the irradiated host mouse, where they reconstitute the immune system. This process has some shortcomings, including FACS costs and the technical experience needed to carry it out. In addition, irradiation can adversely affect the health of the mouse, even after the reconstitution of the immune system. For these reasons, the Tsukuba University research group sought to address these falls with a new method.
“BM chimeric mice are extremely useful in the field of immunology,” says Professor Satoshi Yamazaki, lead author of the study. “We wanted to optimize this model to improve animal welfare and reduce the need for specialized equipment.”
The team developed a specific cell culture medium that was used to grow HSPC in the laboratory. This medium was supplemented with certain stimulant molecules, called growth factors and cytokines, which promoted the growth of HSPCs in culture.
“The growth of HSPCs in our newly formulated medium eliminated the need for FACS,” explains Professor Yamazaki. “We could also genetically manipulate HSPCs within this cultural system.”
In addition, the authors explained how these cultured HSPCs can be successfully created in unconditioned immunocompetent receptor mice. That means the host mice there is no need to irradiate them, eliminating the negative experimental and toxic effects associated with this process.
Overall, this innovative approach can be applied to study the immune system in both healthy and diseased states and will help facilitate a more cost-effective, safe, and scientifically rigorous method.
Kiyosumi Ochi et al, Generation of unconditioned chimeric bone marrow mouse by enrichment based on hematopoietic stem cell and progenitor cultures, Communications on Nature (2021). DOI: 10.1038 / s41467-021-23763-z
University of Tsukuba
Citation: Improving Bone Marrow Transplants in Mice to Help Fight Disease (2021, June 11) Retrieved June 11, 2021 at https://medicalxpress.com/news/2021-06-bone-marrow -transplants-mice-disease.html
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