scholarly journals Hematopoietic Stem Cells in Type 1 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Ida Pastore ◽  
Emma Assi ◽  
Moufida Ben Nasr ◽  
Andrea Mario Bolla ◽  
Anna Maestroni ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Biologic Therapy ◽  
Ex Vivo ◽  
Genetically Engineered ◽  
Murine Models ◽  
Humanized Mouse ◽  
Hematopoietic Stem ◽  
Beneficial Effects ◽  
Humanized Mouse Models

Despite the increasing knowledge of pathophysiological mechanisms underlying the onset of type 1 diabetes (T1D), the quest for therapeutic options capable of delaying/reverting the diseases is still ongoing. Among all strategies currently tested in T1D, the use of hematopoietic stem cell (HSC)-based approaches and of teplizumab, showed the most encouraging results. Few clinical trials have already demonstrated the beneficial effects of HSCs in T1D, while the durability of the effect is yet to be established. Investigators are also trying to understand whether the use of selected and better-characterized HSCs subsets may provide more benefits with less risks. Interestingly, ex vivo manipulated HSCs showed promising results in murine models and the recent introduction of the humanized mouse models accelerated the translational potentials of such studies and their final road to clinic. Indeed, immunomodulatory as well as trafficking abilities can be enhanced in genetically modulated HSCs and genetically engineered HSCs may be viewed as a novel “biologic” therapy, to be further tested and explored in T1D and in other autoimmune/immune-related disorders.

Beneficial Effects of Tamoxifen Treatment in Type 1 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2155-P
Author(s):  
JUAN ZHENG ◽  
MOHAMMAD ISHRAQ ZAFAR ◽  
LULU CHEN ◽  
XIN GUO ◽  
XIAOMING LI
Keyword(s):  
Type 1 Diabetes ◽  
Tamoxifen Treatment ◽  
Beneficial Effects

scholarly journals Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 776
Author(s):  
Kazutaka Terahara ◽  
Ryutaro Iwabuchi ◽  
Yasuko Tsunetsugu-Yokota
Keyword(s):  
Mouse Models ◽  
Humanized Mice ◽  
Lymphoid Tissues ◽  
Humanized Mouse ◽  
Hiv Pathogenesis ◽  
Hematopoietic Stem ◽  
Critical Issues ◽  
In Vivo Animal Models ◽  
Humanized Mouse Models

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.

Islet Transplantation on Biodegradable Polymer Scaffolds for Type 1 Diabetes in Syngeneic and Xenogeneic Murine Models

2011 ◽  
pp. P1-497-P1-497
Author(s):  
Romie F Gibly ◽  
Xiaomin Zhang ◽  
Dixon B Kaufman ◽  
William L Lowe ◽  
Lonnie D Shea
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Biodegradable Polymer ◽  
Murine Models ◽  
Polymer Scaffolds

scholarly journals Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Takuya Yamaguchi ◽  
Ikumi Katano ◽  
Iyo Otsuka ◽  
Ryoji Ito ◽  
Misa Mochizuki ◽  
...  
Keyword(s):  
Mouse Models ◽  
Complement C3 ◽  
Humanized Mouse ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Human Red Blood Cells ◽  
Mouse Macrophages ◽  
C3 Gene ◽  
Humanized Mouse Models

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.

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