Establishment and identification of an immune-humanized mouse model of prostate cancer
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1. Medical College of Yan’an University, Yan’an 716000, China. 2. Laboratory Animal Center, the Air Force Medical University, Xi’an 710032

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    Abstract:

    Objective An ideal animal model for the study of prostate cancer (Pca) immunotherapy is needed. We aimed to establish a mouse model humanized for the immune system and then transplant these mice with human Pca cells. Methods To humanize mice with a reconstructed human immune system, peripheral blood mononuclear cells (PBMCs) were separated from fresh human peripheral blood by density gradient centrifugation and injected into NOD-scid Il2rg- / - mice via the caudal vein. Peripheral blood from these mice was collected at the 3rd, 4th, 5th and 6th weeks following injection, and dynamic changes in human CD45+CD3+ T cells were monitored using flow cytometry analysis. At the 3rd week after humanization, cells from the Pca cell line 22Rv1 were subcutaneously implanted into the right flank of humanized mice. Tumor growth was monitored twice a week. When the tumor grew to about 1000 mmP>3P> , the mice were euthanized. The infiltration of human immune cells in the peripheral blood, spleen and tumor tissues of humanized mice was analyzed by flow cytometry, immunohistochemistry (IHC) and hematoxylin and eosin (HE) staining. Results High levels of CD45+CD3+ T cells were detected in the peripheral blood of mice from 3 to 6 weeks after PBMC transplantation. The mice were euthanized at the 6th week and the result of HE and IHC staining demonstrated that the spleen and tumor tissues of the mice were infiltrated by human immune cells CD4+ and CD8+ T cells. Conclusions The immune-humanized mouse model of Pca was successfully established. This model showed high levels of human immune T cells in the peripheral blood, spleen and Pca tissues, laying a foundation for the construction of an ideal preclinical model of immunotherapy for Pca.

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History
  • Received:July 13,2020
  • Revised:
  • Adopted:
  • Online: February 05,2021
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