Improving bone marrow transplants in mice to help fight disease

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To study the immune system of human health and illness, scientists generally use genetic manipulation of mouse hematopoietic stem cells and progenitor cells (HSPCs) as a powerful model system. These studies are of great value in the fight against many human illnesses. However, the current procedure is complicated, time consuming and expensive.

In a new study published in Nature CommunicationsResearchers at the University of Tsukuba have developed new technologies that have the potential to overcome the limitations associated with these models. Bone marrow (BM) Chimeric mouse. This system allows scientists to observe and investigate how genetic changes affect the phenotype and behavior of immune cells in a physiological environment.

The first step in generating BM chimeric mice is to use irradiation Immune system Of the host mouse. BM is then obtained from donor mice and HSPC is isolated using a process called fluorescence activated cell sorting (FACS). The HSPC is then genetically engineered and transplanted into irradiated host mice, where it reconfigures the immune system. This process has several drawbacks, including the cost of FACS and the technical expertise required to do so. In addition, irradiation can adversely affect the health of mice, even after the immune system has been reconstituted. For these reasons, the University of Tsukuba research group sought to address these dips in new ways.

“BM chimeric mice are very useful in the field of immunology,” says Professor Satoshi Yamazaki, a senior author of the study. “We wanted to optimize this model to improve animal welfare and reduce the need for specialized equipment.”

The team has developed a specific cell culture medium used to grow HSPC in the lab. In this medium Growth factors Cytokines that promote the growth of HSPC in culture.

“The growth of HSPC in newly formulated media has eliminated the need for FACS,” explains Professor Yamazaki. “You can also genetically engineer HSPC within this culture system.”

In addition, the authors described how to successfully transplant these cultured HSPCs into unconditional immunocompetent recipient mice.This is the host mouse or rat No irradiation is required, eliminating the experimental and toxic adverse effects associated with this process.

Overall, this groundbreaking approach can be applied to study the immune system in both healthy and illness states, facilitating a more cost-effective, safe and scientifically rigorous method. Useful for.

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For more information:
Generation of unconditional bone marrow chimeric mice using culture-based enrichment of hematopoietic stem cells and progenitor cells, by Ochiseisumi et al., Nature Communications (2021). DOI: 10.1038 / s41467-021-23763-z

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