
Graft-versus-host disease (GvHD) is a serious, potentially life-threatening complication that can occur after allogeneic hematopoietic stem cell transplantation. It arises when donor immune cells attack the recipient’s tissues, leading to systemic inflammation and damage to organs such as the skin, liver, and gastrointestinal tract.
TransCure bioServices offers a robust humanized mouse model of GvHD using highly immunodeficient mice engrafted with human PBMCs. Upon transfer of allogeneic human PBMCs, mice develop hallmark clinical symptoms and immune activation patterns that closely resemble human GvHD, including T cell activation, weight loss and organ infiltration.
Main characteristics
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Disease Monitoring
Mice are monitored daily for signs of distress. GVHD symptoms are recorded 3-5 times per week for 8-10 weeks. Besides survival, scoring is based on animal body weight loss, posture, activity, fur texture, skin integrity and paleness.
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Human T Cell Activation and Proliferation
Blood Immunophenotyping is performed by flow cytometry to analyse CD4+ and CD8+ human T cell proliferation and activation. Flow cytometry panel (including intra-cellular staining) to be tailored based on study sponsor request.
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Organ Infiltration by Human Immune Cells
Major organs (spleen, liver, intestines,...) are collected, dissociated and analyzed by flow cytometry to characterize human immune cell infiltration based on study sponsor request.
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PBMC Donor Selection
Short pilot study could be conducted to select the most appropriate PBMCs donors based on clinical symptom severity and/or blood immunophenotyping.
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Treatment Modalities
Depending on the scientific goals, PBMCs can be pre-treated in vitro before engraftment, or animals can receive prophylactic or therapeutic treatment a few days after engraftment. This timing allows for randomization based on flow cytometry data.
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Positive Controls
Positive controls or standard-of-care (SOC) treatments are used to validate the model’s responsiveness and provide a benchmark for evaluating new therapies. Here are common examples: Cyclosporine, Ruxolitinib and corticosteroids.
Applications
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Human PBMCs (10 millions) from healthy donors (3 donors) were injected I.P. in NCG mice.
- Cyclosporin-A significantly reduced the mortality and the global clinical score as compared to the vehicle group (saline solution)
- Circulating CD8+ T lymphocytes are decreased by Cyclosporin-A treatment
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The right mouse model for your research experimentation
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Human Immune System Mouse Model
Evaluate both the efficacy and immunotoxicity of your lead candidate using a fully reconstituted human immune system, generated by engrafting CD34+ hematopoietic stem cells into highly immunodeficient mice.
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Contact usKnow everything about the GvHD Mouse Model
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How many PBMC are engrafted ?
The standard number of engrafted PBMCs is 10 million cells per mouse. However, this can be adjusted upon request to either moderate or intensify GvHD symptoms, depending on the study’s specific objectives and desired disease severity. -
What type of mouse strain are engrafted ?
The studies are usually carried out in female NOD-Prkdcem26Cd52Il2rgem26Cd22/NjuCrl (NCG) immunodeficient mouse strain. Other mouse strains could be used based on request. -
What is the best route to engraft PBMCs ?
Our internal data indicate that the two routes of engraftment lead to GvHD but variability is lower when tha PBMCs are injected i.p. -
What is the usual number of mice per group
We recommend using a minimum of 6 mice per group to ensure statistical robustness. If the study design requires sacrificing satellite animals at earlier time points, the group size can be increased accordingly to maintain sufficient power for endpoint analyses. -
Do you irradiate the animal prior engrafting the PBMC ?
Our models have been developed and validated without the need for irradiation, thanks to the high level of immunodeficiency in NCG mice.
You have more questions ?
If you have further questions or would like to discuss how our GvHD model can be tailored to your specific research needs, our scientific team is here to help. We’re committed to providing clear, responsive support and working closely with you to design studies that align with your objectives. Don’t hesitate to reach out - we’re always happy to share our expertise and explore solutions together.
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