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.

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.

scholarly journals Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice

2015 ◽  
Vol 37 (4) ◽  
pp. 1355-1368 ◽  
Author(s):  
Zhen Gong ◽  
Hanzi Xu ◽  
Yiping Su ◽  
Wangfei Wu ◽  
Lin Hao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune System ◽  
Peripheral Blood ◽  
Human Lymphocytes ◽  
Xenograft Model ◽  
Human Bladder Cancer ◽  
Human Immune System ◽  
Human Bladder ◽  
Immunodeficient Mice ◽  
Human Immune

Background/Aims: The aim of this study was to develop a novel model by transplanting human bladder cancer xenografts into humanized immunodeficient mice (SCID). Methods: The animals first underwent sublethal irradiation and then were subjected to simultaneous transplantation of human lymphocytes (5 × 107 cells/mouse i.p.) and human bladder cancer cells (3 × 106 cells/mouse s.c.). Results: The xenografts developed in all 12 mice that had received bladder cancer BIU-87 cells, and the tumor specimens were evaluated histologically. All 6 model mice expressed human CD3 mRNA and/or protein in the peripheral blood, spleens and xenografts. The mean proportion of human CD3+ cells was 19% with a level of human IgG 532.4µ/ml in the peripheral blood at Week 6 after transplant inoculation. The re-constructed human immune system in these mice was confirmed to be functional by individual in vitro testing of their proliferative, secretory and cytotoxic responses. Conclusion: The successful engraftment of the human bladder cancer xenografts and the establishment of the human immune system in our in vivo model described here may provide a useful tool for the development of novel therapeutic strategies targeting at bladder cancer.

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 Mesenchymal Stem Cells in COVID-19: A Journey from Bench to Bedside

2020 ◽  
Vol 52 (1) ◽  
pp. 24-35
Author(s):  
Kamal Kant Sahu ◽  
Ahmad Daniyal Siddiqui ◽  
Jan Cerny
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Therapeutic Option ◽  
Antiviral Agent ◽  
In Vitro Models ◽  
Human Immune System ◽  
Economic Sectors ◽  
Human Immune

Abstract The COVID-19 pandemic has led to a major setback in both the health and economic sectors across the globe. The scale of the problem is enormous because we still do not have any specific anti-SARS-CoV-2 antiviral agent or vaccine. The human immune system has never been exposed to this novel virus, so the viral interactions with the human immune system are completely naive. New approaches are being studied at various levels, including animal in vitro models and human-based studies, to contain the COVID-19 pandemic as soon as possible. Many drugs are being tested for repurposing, but so far only remdesivir has shown some positive benefits based on preliminary reports, but these results also need further confirmation via ongoing trials. Otherwise, no other agents have shown an impactful response against COVID-19. Recently, research exploring the therapeutic application of mesenchymal stem cells (MSCs) in critically ill patients suffering from COVID-19 has gained momentum. The patients belonging to this subset are most likely beyond the point where they could benefit from an antiviral therapy because most of their illness at this stage of disease is driven by inflammatory (over)response of the immune system. In this review, we discuss the potential of MSCs as a therapeutic option for patients with COVID-19, based on the encouraging results from the preliminary data showing improved outcomes in the progression of COVID-19 disease.

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