Humanized Immune System Mouse Models

Q: What is the difference between PBMC and HSC humanized immune system mice?

PBMC humanized immune system mice receive mature human immune cells, mostly T cells. They engraft in about 3 weeks but develop GvHD, so studies last 2–4 weeks. HSC (CD34+) models receive stem cells that develop into multiple immune lineages. They take about 8 weeks to engraft but support studies of 6+ months with low GvHD risk.

Q: Why do PBMC-humanized mice develop severe Graft-versus-Host Disease (GvHD), while HSC-reconstituted mice rarely do?

The mature donor T cells in PBMCs recognize mouse MHC molecules as foreign and attack mouse tissues, which limits PBMC studies to about 2–4 weeks. In HSC humanized immune system mice, new human T cells develop in the mouse thymus and undergo negative selection. They tolerate the host, so GvHD risk is low and studies often run 6 months or longer.

Q: What are the advantages of neonatal HSC reconstitution in NKG mice?

Cyagen’s optimized neonatal HSC reconstitution process offers: ·High post-irradiation survival ·Reliable intravenous injection ·High reconstitution success ·More animals generated from a single donor ·Broader reconstitution of human immune-cell subtypes HSC reconstitution requires sublethal irradiation, a longer development period, and higher costs. It is best suited to studies involving multiple immune-cell populations or complex antitumor mechanisms.

Q: How are humanized immune system mice generated?

Common approaches include: HSC transplantation: Human CD34+ hematopoietic stem cells generate multiple immune-cell lineages. PBMC transplantation: Mature human immune cells provide rapid, short-term immune reconstitution. Human thymus transplantation: Supports human T-cell development, often together with HSC transplantation. Spleen or lymph-node transplantation: Provides additional human immune-cell development and functional support.

Q: Do NKG mice exhibit T-, B-, or NK-cell leakage?

NKG mice carry the Prkdc scid mutation, which impairs T- and B-cell development, together with an Il2rg knockout, which severely disrupts NK-cell development. Cyagen regularly monitors colony genetics, immune function, health, and breeding performance to maintain model quality.

Q: How do tumors grow in NKG mice?

NKG mice support efficient tumor engraftment, high tumor burden, and relatively long survival in many xenograft models. In one THP-1 intravenous model, Cyagen NKG mice showed detectable tumor burden by Day 3 and survived for 33 days, compared with 14 days for a comparator strain. Because growth rates vary by cell line, a pilot study is recommended to confirm engraftment, tumor growth, and the appropriate experimental timeline. For PBMC-humanized models, the interval between PBMC and tumor-cell transplantation should also be optimized.

Q: Do NKG mice develop spontaneous tumors or diabetes?

Spontaneous tumors are rare, although isolated cases of lymphoma may occur. NKG mice do not typically develop spontaneous type 1 diabetes because they lack functional T and B cells capable of attacking pancreatic beta cells. However, metabolic abnormalities resembling type 2 diabetes may develop under specific experimental conditions, such as a high-fat diet.

Humanized immune system mice are immunodeficient mice engrafted with human immune cells, allowing researchers to study human immune responses and test immunotherapies in vivo. Cyagen builds these models by transplanting human PBMCs or HSCs into NKG mice. Developed with neonatal engraftment, our next-generation huHSC-NKG-ProF model reconstitutes both lymphoid (T, B, NK) and myeloid (DC, monocyte, macrophage, granulocyte) lineages.

Broad Research Applications

Support studies in immuno-oncology, immune checkpoint inhibitors, ADCC, CAR-T and CAR-NK therapies, graft-versus-host disease, and myeloid-targeted drug development.

Rapid and Efficient Humanization

Selected models achieve human immune cell engraftment within three weeks, while advanced HSC models can reach 40–60% humanization by eight weeks.

Flexible Immune Profiles

Choose from PBMC- and HSC-based models with T-cell-dominant, multilineage, NK-cell, or myeloid-focused immune reconstitution to match specific research needs.

Overview

Product

FAQs

Overview

PBMC- and HSC-Based Humanized Immune System Mice

Cyagen offers a comprehensive portfolio of humanized immune system mice developed through PBMC or HSC (CD34+) transplantation. PBMC models deliver rapid, T cell–dominant reconstitution for short-term studies, while HSC models provide advanced multilineage engraftment for long-term research. Depending on the model, each immune-humanized mouse can support the reconstitution of human T, B, NK, myeloid and other immune cell populations, enabling fit-for-purpose studies in immuno-oncology, immune checkpoint therapy, ADCC, CAR-T and CAR-NK research, graft-versus-host disease and other translational applications.

PBMC vs. HSC (CD34+): Choosing the Right Humanized Mouse Models for Immune Research
The human cells you engraft decide which immune lineages develop and how long your study can run. Here is how the two approaches compare.

PBMC-Humanized Mice (huPBMC-NKG)
huPBMC-NKG mice are engrafted with human PBMCs and develop a mature human T cell compartment within about three weeks. They are the fastest route to humanized immune system mice when your therapy acts on mature T cells.
- Human cell source: Peripheral blood mononuclear cells (mature immune cells)
- Reconstituted lineages: Mainly mature human T cells
- Time to engraftment: About 3 weeks
- Typical study window: 2–4 weeks, limited by GvHD
- GvHD risk: High, because donor T cells attack mouse tissues

Best for
- Short-term efficacy of T cell engagers, bispecific antibodies and immune checkpoint inhibitors
- Fast in vivo screening before committing to long-term HSC-humanized mouse studies
- GvHD modeling and testing of immunosuppressive drugs

HSC (CD34+)-Humanized Mice (huHSC-NKG Series)
HSC (CD34+)-humanized NKG models are engrafted with human CD34+ hematopoietic stem cells, which give rise to multiple human immune lineages inside the mouse. Because the new human T cells are educated in the mouse thymus, these immune-humanized mice carry a low GvHD risk and support studies lasting six months or longer. For short-term T cell studies, PBMC-humanized mouse models are the faster option.

- Human cell source: CD34+ hematopoietic stem cells
- Reconstituted lineages: Multilineage T, B and NK cells, plus myeloid cells in ProF and ProM
- Time to engraftment: About 8 weeks, reaching 40–60% humanization
- Typical study window: Often 6 months or longer
- GvHD risk: Low, because human T cells are educated in the mouse thymus

Best for:
- Long-term immuno-oncology, cell therapy, ADCC, and NK- or myeloid-targeted drugs
- Immune checkpoint inhibitors and vaccines
- Autoimmunity, PK and toxicity studies

Explore Ready-to-Use Mouse Models

Discover over 18,000 validated mouse strains—including knockout, conditional knockout, and humanized models—covering 20+ research areas such as oncology, neurology, and metabolism. All models are supported by detailed genotype data and guaranteed quality, helping you fast-track discovery with confidence.

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Base Strain

Catalog Number

Catalog Number	Name	Base Strain	Research Application
C001544	huHSC-NKG-ProM	NKG	Tumor Immunology Research: Suitable for drug types such as immune checkpoint inhibitors and those with targets on myeloid cells, for example, combining a PD-1 monoclonal antibody with drugs that affect Macrophage polarization; Autoimmune Disease Research: Evaluation of the pathogenesis of autoimmune diseases and potential therapeutic strategies; Drug Metabolism and Toxicity Research: Assessment of the pharmacokinetic properties and toxic effects of candidate compounds in vivo.
C001543	huHSC-NKG-ProF	NKG	Tumor Immunology Research: Development of drugs such as immune checkpoint inhibitors, tumor vaccines, allogeneic cell therapies, and oncolytic viruses, as well as investigations into mechanisms that reverse T cell exhaustion, antibody-dependent cellular cytotoxicity (ADCC), and tumor-specific immunity； Autoimmune Disease Research: Evaluation of the mechanisms underlying the onset of autoimmune diseases and the exploration of therapeutic strategies； Drug Metabolism and Toxicity Research: Assessment of candidate compounds' pharmacokinetic properties and toxic effects in vivo.
C001545	huHSC-NKG-ProN	NKG	Tumor Immunology Research: Suitable for research on immune checkpoint inhibitors, ADCC (Antibody-Dependent Cell-mediated Cytotoxicity) mechanisms, and in vivo CAR-NK cell therapy; Drug Metabolism and Toxicity Research: Assessment of the pharmacokinetic properties and toxic effects of candidate compounds in vivo.
C001526	huHSC-NKG-hIL15	NKG	Research on the human immune system, haematopoietic system; Human-derived cell line xenograft (CDX) and patient-derived xenograft (PDX); NK cell development mechanism studies, NK cell-related tumor immunotherapy development, and antibody-dependent NK cell-mediated toxicity (ADCC) studies.
C001328	huHSC-NKG	NKG	Research on the immune system and tumor immunity; Research on hematopoietic development and blood diseases; Research on infectious diseases such as HIV and AIDS; Research on tumor transplantation and anti-tumor drug efficacy.
C001329	huPBMC-NKG	NKG	Short-term studies requiring mature T cells in the fields of tumor immunity, Hematopoiesis, and gene therapy for hematologic and infectious diseases.

FAQs

Frequently Asked Questions (FAQs)

What is the difference between PBMC and HSC humanized immune system mice?

Why do PBMC-humanized mice develop severe Graft-versus-Host Disease (GvHD), while HSC-reconstituted mice rarely do?

What are the advantages of neonatal HSC reconstitution in NKG mice?

How are humanized immune system mice generated?

Do NKG mice exhibit T-, B-, or NK-cell leakage?

How do tumors grow in NKG mice?

Do NKG mice develop spontaneous tumors or diabetes?

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