huHSC-NCG

huHSC-NCG mice are generated by implanting Hematopoietic Stem Cells (CD34+HSC) into GemPharmatech's severe immunodeficient NCG mice. The transplanted HSC in irradiated NCG mice then differentiates into a variety of hematopoietic or immune cells, including T cells, B cells, and NK cells. With a long survival cycle and stable reconstituted human immune system, this model can be used for long-term in vivo studies for testing drug efficacy, making it an ideal model for preclinical drug evaluation.


Strategy

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Applications

  • Preclinical anti-tumor efficacy study and safety evaluation

  • Testing of immuno-oncology therapies


Supporting data

1. Detection of the marrow clearing effect in NCG mice

    Without irradiation                                With irradiation

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Irradiation can eliminate the hematopoietic stem cells in the bone marrow, thereby improving the level of reconstruction after transplantation of human HSC. The results showed that the proportion of mCD45+mCD117+ cell population after irradiation was 1.11%, which was significantly lower than the non-irradiated group (13.5%). This result suggests that 150 cGys dose irradiation of 6-7 weeks NCG mice can achieve the desired marrow clearing effect.


2. The survival curve and the body weight change of the huHSC-NCG

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The huHSC-NCG mice can survive more than 37 weeks. In the first period, the body weight of huHSC-NCG mice tended to increase and was not significantly different from that of non-irradiated NCG mice that did not undergo HSC reconstitution. Over time, the body weight of huHSC-NCG mice decreased. By the end of the experiment, it was significantly lower than that of NCG mice that had not undergone irradiation and HSC reconstitution (***, P < 0.001). Overall, the body weight of huHSC-NCG mice increased over time without significant weight loss during long-term immune reconstitution, making this a good model for long-term investigations. Data are shown as mean±SEM.


3. The human immune reconstitution level of the huHSC-NCG mice

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The human immune cell levels in peripheral blood of huHSC-NCG mice were detected by flow cytometry. These are primarily T cells, many immature B cells, and a modest number of NK cells. 


4. The reconstitution levels of humanized immune cells in the huHSC-NCG mice at week 16

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Flow cytometry of huHSC-NCG mice peripheral blood at week 16 revealed that a range of human-derived immune cells could be recognized, with the  proportion of human leukocytes at more than 20%, indicating that the humanized model of huHSC-NCG was successfully established in this experiment.


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