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Mouse models with human immunity and their application in biomedical research.

Zhang B, Duan Z, Zhao Y - J. Cell. Mol. Med. (2008)

Bottom Line: Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism.Peripheral constitution of human immunity in SCID or Rag() mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved.The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.

View Article: PubMed Central - PubMed

Affiliation: Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT
Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag)() mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Rag() mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non-genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.

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The different efficiency of engrafting human HSCs or immune cells in various immunodeficient mouse recipients.
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fig02: The different efficiency of engrafting human HSCs or immune cells in various immunodeficient mouse recipients.

Mentions: NOD/SCID mice are created by backcrossing the SCID mutation into the NOD/LtSz mice, which have less residual immunity than SCID mice, since NOD mice have defects in the complement pathway, macrophage function and NK cell activity [34]. NOD/Shi-SCID mice also have seriously immune functional impairments similar to NOD/LtSz-SCID mice [35, 36]. The innate immune defects in NOD/LtSz-SCID or NOD/Shi-SCID mice might well account for increased human xenograft survival in vivo[37–40]. CD47 can efficiently protect target cells from phagocytosis by macrophages via reacting with signal regulatory protein α(SIRPα) expressed on effector macrophages [41, 42]. However, in widely disparate xenogeneic combinations, haematopoietic cells can be vigorously engulfed by xenogeneic macrophages due to inefficient interaction between CD47 on the xenogeneic target cells and SIRPaon macrophages [41, 43]. It has been reported that human CD47 cross reacts with SIRPα in NOD mice, but not with SIRPα of other mouse stains [44], which indicates that the improved engraftment of human haematopoietic cells in immunodeficient mice with a NOD genetic background may, at least partially, be due to the functional matching of CD47/SIRPα phagocytosis-inhibiting pathway between human beings and mice in this combination. Furthermore, the NOD/SCIDβ2M mice, which severely lack NK cell activity, are developed and available [4, 45]. NOD/SCIDβ2M mice have higher engraftment of human immune cells compared with other immunodeficient mice such as SCID or NOD/SCID mice after a single i.p. transfer of human peripheral blood lymphocytes (PBLs) (Fig. 2) [46].


Mouse models with human immunity and their application in biomedical research.

Zhang B, Duan Z, Zhao Y - J. Cell. Mol. Med. (2008)

The different efficiency of engrafting human HSCs or immune cells in various immunodeficient mouse recipients.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496103&req=5

fig02: The different efficiency of engrafting human HSCs or immune cells in various immunodeficient mouse recipients.
Mentions: NOD/SCID mice are created by backcrossing the SCID mutation into the NOD/LtSz mice, which have less residual immunity than SCID mice, since NOD mice have defects in the complement pathway, macrophage function and NK cell activity [34]. NOD/Shi-SCID mice also have seriously immune functional impairments similar to NOD/LtSz-SCID mice [35, 36]. The innate immune defects in NOD/LtSz-SCID or NOD/Shi-SCID mice might well account for increased human xenograft survival in vivo[37–40]. CD47 can efficiently protect target cells from phagocytosis by macrophages via reacting with signal regulatory protein α(SIRPα) expressed on effector macrophages [41, 42]. However, in widely disparate xenogeneic combinations, haematopoietic cells can be vigorously engulfed by xenogeneic macrophages due to inefficient interaction between CD47 on the xenogeneic target cells and SIRPaon macrophages [41, 43]. It has been reported that human CD47 cross reacts with SIRPα in NOD mice, but not with SIRPα of other mouse stains [44], which indicates that the improved engraftment of human haematopoietic cells in immunodeficient mice with a NOD genetic background may, at least partially, be due to the functional matching of CD47/SIRPα phagocytosis-inhibiting pathway between human beings and mice in this combination. Furthermore, the NOD/SCIDβ2M mice, which severely lack NK cell activity, are developed and available [4, 45]. NOD/SCIDβ2M mice have higher engraftment of human immune cells compared with other immunodeficient mice such as SCID or NOD/SCID mice after a single i.p. transfer of human peripheral blood lymphocytes (PBLs) (Fig. 2) [46].

Bottom Line: Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism.Peripheral constitution of human immunity in SCID or Rag() mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved.The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.

View Article: PubMed Central - PubMed

Affiliation: Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT
Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag)() mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Rag() mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non-genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.

Show MeSH
Related in: MedlinePlus