To examine the immune system in human well being and illness, scientists generally use the genetic manipulation of mouse hematopoietic stem and progenitor cells (HSPCs) as a robust mannequin system. These research have been extraordinarily beneficial within the battle towards a lot of human illnesses. However, the present procedures are complicated, time-consuming, and costly.
In a brand new examine printed in Nature Communications, researchers on the University of Tsukuba have developed a novel approach that has the potential to beat the constraints related to these fashions, that are often known as bone marrow (BM) chimeric mice. This system permits scientists to look at and examine how genetic alterations have an effect on immune cell phenotypes and behaviors in a physiological setting.
The first step of producing BM chimeric mice is utilizing irradiation to destroy the immune system of the host mouse. BM is then acquired from a donor mouse and HSPCs are remoted utilizing a course of referred to as fluorescence-activated cell sorting (FACS). Next, the HSPCs are genetically manipulated after which engrafted within the irradiated host mouse, the place they reconstitute the immune system. This course of has some shortcomings, together with the expense of FACS and the technical experience wanted to carry out it. Furthermore, irradiation can detrimentally have an effect on the mouse’s well being, even following immune system reconstitution. For these causes, the University of Tsukuba analysis group aimed to deal with these downfalls with a brand new methodology.
“BM chimeric mice are extremely useful in the immunology field,” says Professor Satoshi Yamazaki, senior writer of the examine. “We wanted to optimize this model to improve animal welfare and reduce the need for specialized equipment.”
The workforce developed a particular cell tradition medium that was used to develop HSPCs within the lab. This medium was supplemented with sure stimulating molecules, referred to as growth factors and cytokines, that promoted the expansion of the HSPCs in tradition.
“Growth of HSPCs in our newly formulated medium eliminated the need for FACS,” explains Professor Yamazaki. “We could also genetically manipulate HSPCs within this culture system.”
Additionally, the authors defined how these cultured HSPCs could be efficiently engrafted in non-conditioned immunocompetent recipient mice. This implies that the host mice don’t have to be irradiated, eliminating the destructive experimental and poisonous results related to this course of.
Overall, this groundbreaking method could be utilized to review the immune system in each wholesome and diseased states and can assist to facilitate a cheaper, secure, and scientifically rigorous methodology.
Kiyosumi Ochi et al, Non-conditioned bone marrow chimeric mouse era utilizing culture-based enrichment of hematopoietic stem and progenitor cells, Nature Communications (2021). DOI: 10.1038/s41467-021-23763-z
University of Tsukuba
Improving bone marrow transplants in mice to assist battle illness (2021, June 11)
retrieved 11 June 2021
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