Human CD34⁺ Hematopoietic Stem Cell-Engrafted NSG Mice: Morphological and Immunophenotypic Features

Area of Science:

• Immunology
• Pathology
• Animal Models

Background:

• Immunodeficient mice engrafted with human immune cells enhance the translatability of animal models for human disease research.
• Current immunophenotyping relies heavily on fluorescent activated cell sorting (FACS), with limited information on morphological aspects and histologic lesions.

Purpose of the Study:

• To histologically examine young NSG mice, both naive and engrafted with human hematopoietic stem cells (HSC).
• To compare quantitative immunohistochemistry with FACS data for human and murine cell compartment identification.
• To characterize common pathological features and lesions in this model system.

Main Methods:

• Histological examination of 3- to 6-month-old NSG mice (naïve or engrafted with CD34+ human HSC).
• Quantitative immunohistochemistry to identify human (hCD45+) and murine cell compartments.
• Comparison of histological findings with FACS data.

Main Results:

• NSG mice showed incidental findings; one had lymphoblastic lymphoma. Engrafted mice frequently developed nephropathy, ovarian atrophy, cataract, and retinal abnormalities.
• Multisystemic granulomatous inflammatory infiltrates (human macrophages and T cells) occurred in 20%, causing 7% mortality/morbidity.
• Human cell engraftment levels (hCD45+) in lymphoid organs varied and did not consistently correlate with FACS data.

Conclusions:

• This study details common pathological features in young NSG mice post-human HSC engraftment.
• Some observed lesions contribute to morbidity, suggesting morphological assessment at the tissue level can improve immunophenotypic evaluations.
• Tissue-level assessment is crucial for a comprehensive understanding of engraftment and model translatability.