scholarly journals The Utility of Human Immune System Mice for High-Containment Viral Hemorrhagic Fever Research

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 98
Author(s):  
David M. Wozniak ◽  
Kerry J. Lavender ◽  
Joseph Prescott ◽  
Jessica R. Spengler
Keyword(s):  
Immune System ◽  
Mouse Models ◽  
Severe Disease ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Human Immune System ◽  
Immunodeficient Mice ◽  
Hemorrhagic Fevers ◽  
Laboratory Facilities ◽  
Human Immune

Human immune system (HIS) mice are a subset of humanized mice that are generated by xenoengraftment of human immune cells or tissues and/or their progenitors into immunodeficient mice. Viral hemorrhagic fevers (VHFs) cause severe disease in humans, typically with high case fatality rates. HIS mouse studies have been performed to investigate the pathogenesis and immune responses to VHFs that must be handled in high-containment laboratory facilities. Here, we summarize studies on filoviruses, nairoviruses, phenuiviruses, and hantaviruses, and discuss the knowledge gained from using various HIS mouse models. Furthermore, we discuss the complexities of designing and interpreting studies utilizing HIS mice while highlighting additional questions about VHFs that can still be addressed using HIS mouse models.

scholarly journals Recent Advancements and Applications of Human Immune System Mice in Preclinical Immuno-Oncology

2019 ◽  
Vol 48 (2) ◽  
pp. 302-316 ◽  
Author(s):  
Michelle Curran ◽  
Maelle Mairesse ◽  
Alba Matas-Céspedes ◽  
Bethany Bareham ◽  
Giovanni Pellegrini ◽  
...  
Keyword(s):  
Immune System ◽  
New Technologies ◽  
Immune Cell ◽  
Human Immune System ◽  
Immunodeficient Mice ◽  
Graft Versus Host ◽  
Human Immune ◽  
And Function ◽  
Human Cytokines

Significant advances in immunotherapies have resulted in the increasing need of predictive preclinical models to improve immunotherapeutic drug development, treatment combination, and to prevent or minimize toxicity in clinical trials. Immunodeficient mice reconstituted with human immune system (HIS), termed humanized mice or HIS mice, permit detailed analysis of human immune biology, development, and function. Although this model constitutes a great translational model, some aspects need to be improved as the incomplete engraftment of immune cells, graft versus host disease and the lack of human cytokines and growth factors. In this review, we discuss current HIS platforms, their pathology, and recent advances in their development to improve the quality of human immune cell reconstitution. We also highlight new technologies that can be used to better understand these models and how improved characterization is needed for their application in immuno-oncology safety, efficacy, and new modalities therapy development.

scholarly journals Advances in Human Immune System Mouse Models for Personalized Treg-Based Immunotherapies

2021 ◽  
Vol 12 ◽  
Author(s):  
Isabelle Serr ◽  
Maria Kral ◽  
Martin G. Scherm ◽  
Carolin Daniel
Keyword(s):  
Stem Cells ◽  
Immune System ◽  
Personalized Medicine ◽  
Peripheral Blood ◽  
Human Immune System ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Central Target ◽  
Human Immune ◽  
Cancer Immunotherapies

Immunodeficient mice engrafted with a functional human immune system [Human immune system (HIS) mice] have paved the way to major advances for personalized medicine and translation of immune-based therapies. One prerequisite for advancing personalized medicine is modeling the immune system of individuals or disease groups in a preclinical setting. HIS mice engrafted with peripheral blood mononuclear cells have provided fundamental insights in underlying mechanisms guiding immune activation vs. regulation in several diseases including cancer. However, the development of Graft-vs.-host disease restrains relevant long-term studies in HIS mice. Alternatively, engraftment with hematopoietic stem cells (HSCs) enables mimicking different disease stages, however, low frequencies of HSCs in peripheral blood of adults impede engraftment efficacy. One possibility to overcome those limitations is the use of patient-derived induced pluripotent stem cells (iPSCs) reprogrammed into HSCs, a challenging process which has recently seen major advances. Personalized HIS mice bridge research in mice and human diseases thereby facilitating the translation of immunomodulatory therapies. Regulatory T cells (Tregs) are important mediators of immune suppression and thereby contribute to tumor immune evasion, which has made them a central target for cancer immunotherapies. Importantly, studying Tregs in the human immune system in vivo in HIS mice will help to determine requirements for efficient Treg-targeting. In this review article, we discuss advances on personalized HIS models using reprogrammed iPSCs and review the use of HIS mice to study requirements for efficient targeting of human Tregs for personalized cancer immunotherapies.

scholarly journals Human immune system mouse models of Ebola virus infection

2017 ◽  
Vol 25 ◽  
pp. 90-96 ◽  
Author(s):  
Jessica R Spengler ◽  
Joseph Prescott ◽  
Heinz Feldmann ◽  
Christina F Spiropoulou
Keyword(s):  
Immune System ◽  
Virus Infection ◽  
Mouse Models ◽  
Ebola Virus ◽  
Human Immune System ◽  
Human Immune ◽  
Ebola Virus Infection

Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation

Blood ◽  
2006 ◽  
Vol 108 (2) ◽  
pp. 487-492 ◽  
Author(s):  
Ping Lan ◽  
Noriko Tonomura ◽  
Akira Shimizu ◽  
Shumei Wang ◽  
Yong-Guang Yang
Keyword(s):  
Immune System ◽  
Scid Mice ◽  
In Vivo Model ◽  
Human Immune System ◽  
Hematopoietic Stem ◽  
Fetal Thymus ◽  
Xenograft Rejection ◽  
Immunodeficient Mice ◽  
Human Immune

Studies of the human immune system have been limited by the lack of an appropriate in vivo model. For this reason, efforts have been made to develop murine models with a functional human immune system. We report here that cotransplantation of human fetal thymus/liver tissues and CD34+ hematopoietic stem/progenitor cells led to the development of sustained human hematopoiesis and a functional human immune system in immunodeficient NOD/SCID mice. The humanized mice showed systemic repopulation with a comprehensive array of human lymphohematopoietic cells, including T cells, B cells, and dendritic cells, and the formation of secondary lymphoid organs. Furthermore, these mice produce high levels of human IgM and IgG antibodies and mediate strong immune responses in vivo as demonstrated by skin xenograft rejection. Thus, the humanized NOD/SCID mice described in this paper provide a powerful model system to study human immune function.

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