Humanized mice: A brief overview on their diverse applications in biomedical research

Fujiwara, Shigeyoshi

doi:10.1002/jcp.26022

Cited by 60 publications

(40 citation statements)

References 97 publications

(117 reference statements)

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“…e usage of humanized mouse models could overcome the disadvantages of NHPs and other animal models. In particular, the BLT humanized mouse has facilitated pioneering studies of TB pathogenesis, pathology, and vaccines [197,199,201,209]. Although the cost of BLT mice is higher than that of small mammalian animal models such as mice, guinea pigs, and rabbits, the expense of BLT mice is considerably lower than that of NHPs.…”

Section: Resultsmentioning

confidence: 99%

“…Humanized mice (defined as mice engra ed with functional human genes, cells, or tissues) have become an essential tool in validating the results of infectious disease research in recent years because of their small size, easy access, low cost, clear genetic background, and easy manipulation. To date, large numbers of human cells or tissues have been engra ed in mouse models, including immune system components, hepatocytes, skin tissue, pancreatic islets, uterine endometrium, and neural cells [197]. Recently, some new humanized mouse models have been developed to identify potential TB or other vaccine candidates, including humanized NOD/shi-scid/γ c null (NOG) mice [198], NOD/SCID/γ c null (NSG) mice engra ed with human fetal liver and thymus tissues, and CD34 + cells [199], DRAG mice (NSG mice transgenic for human DR4, RRID:IMSR_JAX:017914) [200], HSC-engra ed NSG mice [201], HLA-A2 transgenic NSG-BLT mice [201], and NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice [202].…”

Section: Humanized Transgenic Animal Models Bring New Hope For Tb Vacmentioning

confidence: 99%

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Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis

Gong

Liang

2020

BioMed Research International

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Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, is one of the top ten infectious diseases worldwide, and is the leading cause of morbidity from a single infectious agent. M. tuberculosis can cause infection in several species of animals in addition to humans as the natural hosts. Although animal models of TB disease cannot completely simulate the occurrence and development of human TB, they play an important role in studying the pathogenesis, immune responses, and pathological changes as well as for vaccine research. This review summarizes the commonly employed animal models, including mouse, guinea pig, rabbit, rat, goat, cattle, and nonhuman primates, and their characteristics as used in TB vaccine research, and provides a basis for selecting appropriate animal models according to specific research needs. Furthermore, some of the newest animal models used for TB vaccine research (such as humanized animal models, zebrafish, Drosophila, and amoeba) are introduced, and their characteristics and research progress are discussed.

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Section: Resultsmentioning

confidence: 99%

Section: Humanized Transgenic Animal Models Bring New Hope For Tb Vacmentioning

confidence: 99%

Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis

Gong

Liang

2020

BioMed Research International

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“…In this way, hu-mice permit detailed analyses of a wide range of therapeutics because of the presence of functional human leukocytes. Many previous studies, including our own, have investigated the immunogenic response of humice following cellular therapeutics in various chronic wound models, such as ischemia, cancer, HIV/acquired immune deficiency syndrome, and diabetic ulcers (Fujiwara, 2018;Yang et al, 2013). However, little attention has been given to the role of human leukocyte activity in the regenerative process of cutaneous wounds in vivo.…”

Section: Introductionmentioning

confidence: 99%

Reconstituting Human Cutaneous Regeneration in Humanized Mice under Endothelial Cell Therapy

Yang

Choi

Kim

et al. 2019

Journal of Investigative Dermatology

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Much of our understanding of human biology and the function of mammalian cells in tissue regeneration have been derived from mechanistically and genetically manipulated rodent models. However, current models examining epidermal wound repair fail to address both the cross-species mechanistic and immunogenic differences simultaneously. Herein, we describe a multifaceted approach intended to better recapitulate human skin recovery in rodent models. First, immunodeficient NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice were intravenously inoculated with human hematopoietic stem cells to become, in essence, humanized, and capable of initiating an adaptive immune response. Next, a chimney-shaped mechanical device was implanted onto the excisional wound site to prevent healing by primary intention (contraction) and expedite cell transplantation. Subsequently, cell therapy was administered by transplanting cord bloodederived endothelial progenitor cells or human pluripotent stem cellederived endothelial cells into the wound site to examine the regeneration process at a histological level. This study demonstrates human cutaneous repair in a murine model by addressing both the mechanistic and immunogenic differences in the epidermis. We further show human leukocyte recruitment in damaged tissue and improved healing by secondary intention in the transplanted groups, highlighting the need for useful preclinical animal models to better understand leukocyte function in human (tissue repair and) regeneration.

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“…The humanization of HIS mice improved steadily from mice with “simple” genetic defects that led to immunodeficiency and to which human cells were xenotransplanted, to mice with more complex genetic modifications that received fetal liver, bone marrow and thymus tissue in addition to human stem cells, to additional knockins of human growth factors that supported the reconstitution of more immune cell populations. The history of humanized mice and their optimization [ 201 , 202 , 203 ] as well as an overview of available humanized mouse models, their general advantages and disadvantages, and their applications were excellently reviewed by others [ 199 , 204 , 205 , 206 ].…”

Section: Implications Of Staphylococcal Host Adaptation For Murinementioning

confidence: 99%

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

Mrochen

Oliveira

Raafat

et al. 2020

IJMS

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Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus infection. Major advances towards understanding the pathogenesis of S. aureus diseases have been made using conventional mouse models, i.e., by infecting naïve laboratory mice with human-adapted S.aureus strains. However, the failure to transfer certain results obtained in these murine systems to humans highlights the limitations of such models. Indeed, numerous S. aureus vaccine candidates showed promising results in conventional mouse models but failed to offer protection in human clinical trials. These limitations arise not only from the widely discussed physiological differences between mice and humans, but also from the lack of attention that is paid to the specific interactions of S. aureus with its respective host. For instance, animal-derived S. aureus lineages show a high degree of host tropism and carry a repertoire of host-specific virulence and immune evasion factors. Mouse-adapted S.aureus strains, humanized mice, and microbiome-optimized mice are promising approaches to overcome these limitations and could improve transferability of animal experiments to human trials in the future.

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Humanized mice: A brief overview on their diverse applications in biomedical research

Cited by 60 publications

References 97 publications

Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis

Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis

Reconstituting Human Cutaneous Regeneration in Humanized Mice under Endothelial Cell Therapy

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

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