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huHSC-NCG

Strain:huCD34+HSC-NOD-Prkdcem26Cd52IL2rgem26Cd22/Gpt 

Product namehuHSC-NCG

Strain type:Immune reconstitution

Strain code T037620

Background: NOD-Prkdcem26Cd52IL2rgem26Cd22/Gpt


Strain Features

HSC humanized mice are the powerful models for assessment of new drugs based on immune modulation. These models establish human immune system by engraftment of human hematopoietic stem cells (HSC) into severe immunodeficient mice(e.g. NCG). NCG mice that have been sublethally irradiated are injection with human HSCs derived from umbilical cord blood, bone marrow, fetal liver through tail vein or intraperitoneal, which allow them to develop mature human immune cells with multi-lineage, including T cells, B cells, NK cells and myeloid cells[1]. The engrafted human immune cells with the co-transplanted cancer cells mimic the tumor microenvironment and display immune response manifesting in patients[2,3]. With long survival cycle and stable reconstituted human immune system, the model could be used for long-term in vivo studies for drug effectiveness ,which make it the ideal platform for preclinical drug evaluation.

NCG mice, developed by GemPharmatech Co., Ltd, are one of the severe immunodeficient mice models featured with lacking of T cells, B cells and NK cells, as well as developmental failure of macrophages and dendritic cells, allowing them to be the powerful tools for human immune system reconstitution. Our HSC humanized NCG mice(huHSC-NCG), combined with PDX and CDX models, could facilitate the investigation of tumor progression under human immune modulation, and evaluate drug effectiveness for anti-tumor, especially the immune-based therapeutic strategies for cancer treatment. 

HSC humanization Strategy

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Fig.1 The establishment of huHSC-NCG mice


Application

1. Immuno-oncology therapy

2. Infectious disease research (e.g. HIV)

3. Study of human hematopoietic development


Validation

Figure 1 Body weight changes of huHSC-NCG mice       Figure 2 Survival curve of huHSC-NCG mice      


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The body weight of huHSC-NCG mice was gradually increased during immune reconstitution, and no death of mouse was observed 20 weeks post transplantation.


Figure 3 Immunophenotypes of huHSC-NCG mice

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Peripheral blood were collected at weeks 10,12,14,16 and 18 to characterize immunophenotypes by flow cytometry. During the humanization process, hCD45+ cells have been over 20% since week 10 , in the meanwhile, CD3+ cells were gradually increased and developed CD4+ and CD8+ subpopulation. hCD19+B cells were maintained at high level while CD16/CD56+NK cells displayed lower reconstitution level. Data were presented as mean±SEM.


Figure 4 Typical immune profiling of huHSC-NCG mice

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Multiple human immune cells were detected in mice peripheral blood by flow cytometer, suggesting the humanization of immune system in NCG mice.


References

1.Shultz, L.D., et al., Human Lymphoid and Myeloid Cell Development in NOD/LtSz-scid IL2R null Mice Engrafted with Mobilized Human Hemopoietic Stem Cells. The Journal of Immunology, 2005. 174(10): p. 6477-6489.

2. Seitz, Establishment of a rhabdomyosarcoma xenograft model in human-adapted mice. Oncology Reports, 2010.

3. Wege, A.K., et al., Humanized tumor mice--a new model to study and manipulate the immune response in advanced cancer therapy. Int J Cancer, 2011. 129(9): p. 2194-206.




Time:2020-12-28