huHSC Humanized Model

The huHSC humanized model represents a cornerstone in advanced preclinical immunology. It involves the engraftment of human CD34⁺ hematopoietic stem cells into immunodeficient mice, leading to the de novo development of a diverse, self-renewing, and multi-lineage human immune system. This model provides a unique window into human immune development, function, and long-term interactions with diseases or therapeutics. Leveraging this sophisticated technology, Alfa Cytology's huHSC humanized mouse models are the premier tool for comprehensive, long-term immunotherapy and immunology research. Through our optimized protocols, we achieve stable, systemic, and sustained immune reconstitution, delivering deep, clinically predictive in vivo insights over extended study timelines.

Introduction to huHSC Humanized Model

The core advantage of the huHSC model, compared to short-term models, lies in its completeness and sustainability. It supports the development of functional human T cells in the thymus, the production of human immunoglobulins by B cells, and the collaboration between innate and adaptive immune systems. This makes it particularly suitable for evaluating vaccine immunogenicity, studying immune responses in chronic infections, exploring mechanisms of autoimmune diseases, and testing therapies that require long-term dosing or rely on complex immune cell synergy. A stably reconstituted huHSC model can sustain multi-lineage human immune cells for several months, enabling efficacy studies that span extended periods.

Fig.1 Schematic diagram of the huHSC-CD34⁺-NCG model establishment process.

Characteristics of huHSC Humanized Model

Our Services

Alfa Cytology provides a robust, physiologically relevant huHSC humanized mouse model generation service. Our Hu-Immune™ platform is engineered to recapitulate human immune system development, enabling deep mechanistic insights and long-term therapeutic evaluation for your most challenging research questions in immunology and immuno-oncology.

Our huHSC-34⁺ Humanized Model

The huHSC platform establishes a comprehensive human immune microenvironment through de novo development of immune cells from hematopoietic stem cells.

• Stable Multi-lineage Reconstitution: Achieves approximately 40% human CD45+ cell chimerism with balanced reconstitution of T, B, NK, and myeloid cell populations.
• Extended Study Windows: Supports long-term efficacy evaluation over several months, enabling chronic disease modeling and repeated dosing regimens.
• Enhanced Predictive Value: Recapitulates human-specific immune responses and mechanisms, providing clinically relevant insights for drug development.

Fig.2 huHSC platform: stable immune reconstitution and extended therapeutic.

Workflow for huHSC Humanized Model Studies

Alfa Cytology has established a standardized workflow for huHSC model studies, ensuring exceptional reproducibility and data reliability at every stage, from model generation to final data delivery.

Case Study

Case 1: Evaluation of CLDN18.2 Targeted Therapy in huHSC Model

Overview

Evaluate antitumor efficacy of a CLDN18.2-targeting monoclonal antibody and characterize human immune compartments in a huHSC (CD34⁺) humanized model.

Study Information

• Humanized Model: huHSC-CD34⁺ model on NCG strain.
• Tumor Model: NUGC4 (CLDN18.2⁺) gastric cancer CDX.
• Treatment: CLDN18.2-targeting monoclonal antibody.

Results

• Potent Anti-Tumor Efficacy: The model demonstrated a robust and durable anti-tumor response to the CLDN18.2-targeting antibody.
• Activation of Human Immunity: Immune profiling revealed activation and infiltration of human T cells and NK cells into the tumor microenvironment.
• Mechanistic Insight: The observed immune cell activation correlated with significant tumor growth inhibition, validating the platform's utility for evaluating targeted antibodies in a physiologically relevant, long-term human immune context.

Fig.3 Anti-tumor activity of a CLDN18.2 antibody and human immune compartments in a huHSC (CD34⁺) humanized NCG model.

Case 2: Comparative Validation of Immunotherapy Efficacy Across Models in huHSC Model

Overview

This study conducted a systematic comparison to assess the predictive power of the huHSC model against other common preclinical models for evaluating the efficacy of an immune checkpoint inhibitor over an extended timeline.

Study Information

• Humanized Model: huHSC-CD34⁺ model on NCG background.
• Treatment: An immune checkpoint inhibitor.

Results

• Sustained Therapeutic Effect: The huHSC model uniquely recapitulated a sustained therapeutic effect over time in response to checkpoint blockade.
• Superior Predictive Value: The data underscored its superior value for modeling complex human immuno-oncology dynamics, including long-term memory responses and immune-mediated tumor control.
• Translational Bridge: The model provided a critical translational bridge to the clinic by supporting long-term, systemic human immune system development and enabling the observation of delayed or adaptive immune responses.

Fig.4 Antitumor activity across multiple models and agents.

Why Choose Our huHSC Platform?

• Complete Human Immune Ecosystem: Recapitulates diverse immune cell populations and their interactions
• Extended Study Capability: Supports long-term investigations spanning several months
• Enhanced Translational Value: Provides human-specific insights with clinical relevance
• Robust Technical Support: Expert guidance throughout study design and implementation

Ready to unlock the complexities of human immunology with a model that mirrors human physiology? Alfa Cytology's huHSC humanized models provide the depth and duration you need for groundbreaking discoveries. Contact our scientific team today to discuss how we can support your long-term research goals.

For research use only.