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Featured Topic: Humanized mouse models

Humanized mice – immunodeficient mice engrafted with functional human cells – have become increasingly important for the study of human diseases (Walsh et al, 2017).

Although “classical” mouse studies are extremely important to understand basic biological processes, there are limitations to mouse studies when investigating human biology (Mestas et al., 2004). Especially cancer and cancer immunotherapy research lead to a growing need for faithful mouse models that recapitulate the complexity of human malignancy and immune contexture within the tumor microenvironment (Olson et al., 2018). Human xenograft models, using human cell lines injected into immunodeficient mice, are common models to evaluate cytotoxic therapies in cancer, but do not reflect intra-tumor heterogeneity and should preferably be used in relatively early stages of drug development (Murayama, 2019). PDX models, in which tumor samples obtained from patients are transplanted into immunodeficient mice, resemble better the original tumors in patients and have therefore higher predictive value in drug development studies (Murayama, 2019). Next generation PDX models are additionally engrafted with human immune cells and are valuable models for immune-based therapies (Murayama, 2019).

Histological analysis of humanized mouse models is impeded, as widely used antibodies have often been developed to function in many species and thus do not discriminate between human and mouse components in humanized mouse models.

HistoSure Xenograft Pathology antibodies are specially designed and developed to fill this antibody gap.

 

HistoSure antibodies discriminate between murine and human proliferating cells in a humanized mouse spleen:

Doublestaining of anti-human and anti-mouse Ki67 in humanized mouse spleen

Figure: Immunohistochemical doublestaining of formalin-fixed paraffin embedded mouse spleen engrafted with human CD34+-cells using rabbit anti-human Ki67 (cat. no. HS-398 003; AP-RED, red color) and rat anti-mouse Ki67 (cat. no. HS-398 117; DAB, brown color). Nuclei have been counterstained with haematoxylin (blue). Tissue provided by Charles River

HistoSure antibodies discriminate between murine and human proliferating cells in a humanized mouse spleen:

Figure: Immunohistochemical doublestaining of formalin-fixed paraffin embedded mouse spleen engrafted with human CD34+-cells using rabbit anti-human Ki67 (cat. no. HS-398 003; AP-RED, red color) and rat anti-mouse Ki67 (cat. no. HS-398 117; DAB, brown color). Nuclei have been counterstained with haematoxylin (blue). Tissue provided by Charles River

 
  • Walsh et al., 2017: Humanized mouse models of clinical disease. PMID: 27959627
  • Mestas et al., 2004: Of Mice and Not Men: Differences between Mouse and Human Immunology. PMID: 14978070
  • Olson et al., 2018: Mouse Models for Cancer Immunotherapy Research. PMID: 30309862
  • Murayama 2019: Patient-Derived Xenograft Models of Breast Cancer and Their Application. PMID: 31226846