scholarly journals Abstract 2712: Donor selection strategies to optimize humanized mouse models for the evaluation of T cell engagers

Author(s):  
Liqing Cheng ◽  
Jane Chen ◽  
Qunyan Yu ◽  
Natalia Malkova ◽  
Virna F. Cortez-Retamozo ◽  
...  
2012 ◽  
Vol 14 (8) ◽  
pp. 540-548 ◽  
Author(s):  
Andreas Volk ◽  
Sylvia Hartmann ◽  
Alexander Muik ◽  
Yvonne Geiß ◽  
Christoph Königs ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 476
Author(s):  
Akihiro Mori ◽  
Soichiro Murata ◽  
Nao Tashiro ◽  
Tomomi Tadokoro ◽  
Satoshi Okamoto ◽  
...  

Humanized mouse models have contributed significantly to human immunology research. In transplant immunity, human immune cell responses to donor grafts have not been reproduced in a humanized animal model. To elicit human T-cell immune responses, we generated immune-compromised nonobese diabetic/Shi-scid, IL-2RγKO Jic (NOG) with a homozygous expression of human leukocyte antigen (HLA) class I heavy chain (NOG-HLA-A2Tg) mice. After the transplantation of HLA-A2 human hematopoietic stem cells into NOG-HLA-A2Tg, we succeeded in achieving alloimmune responses after the HLA-mismatched human-induced pluripotent stem cell (hiPSC)-derived liver-like tissue transplantation. This immune response was inhibited by administering tacrolimus. In this model, we reproduced allograft rejection after the human iPSC-derived liver-like tissue transplantation. Human tissue transplantation on the humanized mouse liver surface is a good model that can predict T-cell-mediated cellular rejection that may occur when organ transplantation is performed.


Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 776
Author(s):  
Kazutaka Terahara ◽  
Ryutaro Iwabuchi ◽  
Yasuko Tsunetsugu-Yokota

A variety of humanized mice, which are reconstituted only with human hematopoietic stem cells (HSC) or with fetal thymus and HSCs, have been developed and widely utilized as in vivo animal models of HIV-1 infection. The models represent some aspects of HIV-mediated pathogenesis in humans and are useful for the evaluation of therapeutic regimens. However, there are several limitations in these models, including their incomplete immune responses and poor distribution of human cells to the secondary lymphoid tissues. These limitations are common in many humanized mouse models and are critical issues that need to be addressed. As distinct defects exist in each model, we need to be cautious about the experimental design and interpretation of the outcomes obtained using humanized mice. Considering this point, we mainly characterize the current conventional humanized mouse reconstituted only with HSCs and describe past achievements in this area, as well as the potential contributions of the humanized mouse models for the study of HIV pathogenesis and therapy. We also discuss the use of various technologies to solve the current problems. Humanized mice will contribute not only to the pre-clinical evaluation of anti-HIV regimens, but also to a deeper understanding of basic aspects of HIV biology.


2015 ◽  
Vol 31 (11) ◽  
pp. 583-594 ◽  
Author(s):  
Michael F. Good ◽  
Michael T. Hawkes ◽  
Stephanie K. Yanow

2021 ◽  
Vol 12 ◽  
Author(s):  
Takuya Yamaguchi ◽  
Ikumi Katano ◽  
Iyo Otsuka ◽  
Ryoji Ito ◽  
Misa Mochizuki ◽  
...  

Despite recent advances in immunodeficient mouse models bearing human red blood cells (hRBCs), the elimination of circulating hRBCs by residual innate immune systems remains a significant challenge. In this study, we evaluated the role of mouse complement C3 in the elimination of circulating hRBCs by developing a novel NOG substrain harboring a truncated version of the murine C3 gene (NOG-C3ΔMG2-3). Genetic C3 deletion prolonged the survival of transfused hRBCs in the circulation. Chemical depletion and functional impairment of mouse macrophages, using clodronate liposomes (Clo-lip) or gadolinium chloride (GdCl3), respectively, further extended the survival of hRBCs in NOG-C3ΔMG2-3 mice. Low GdCl3 toxicity allowed the establishment of hRBC-bearing mice, in which hRBCs survived for more than 4 weeks with transfusion once a week. In addition, erythropoiesis of human hematopoietic stem cells (hHSCs) was possible in NOG-C3ΔMG2-3/human GM-CSF-IL-3 transgenic mice with Clo-lip treatment. These findings indicate that mouse models harboring hRBCs can be achieved using NOG-C3ΔMG2-3 mice, which could facilitate studies of human diseases associated with RBCs.


2014 ◽  
Vol 410 ◽  
pp. 3-17 ◽  
Author(s):  
Michael A. Brehm ◽  
Michael V. Wiles ◽  
Dale L. Greiner ◽  
Leonard D. Shultz

2013 ◽  
Vol 18 (23-24) ◽  
pp. 1200-1211 ◽  
Author(s):  
Nico Scheer ◽  
Mike Snaith ◽  
C. Roland Wolf ◽  
Jost Seibler

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