Related Experiment Video
Updated: Jun 16, 2025
Production of Humanized Mouse via Thymic Renal Capsule Grafting, CD34+ Cells Injection, and Cytokine Delivery
Published on: September 27, 2021
Efficient generation of human immune system rats using human CD34+ cells
Séverine Ménoret1, Florence Renart-Depontieu2, Gaelle Martin2
1Nantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, F-44000 Nantes, France; INSERM, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes Université, Nantes, France.
Researchers developed a new method to create human immune system (HIS) rats by injecting human stem cells into newborn rats. These HIS rats show a more human-like immune response, offering a promising new model for immunotherapy research.
Area of Science:
- Immunology
- Transplantational Research
- Hematopoietic Stem Cell Biology
Background:
- Human immune system (HIS) mice are crucial for in vivo immunotherapy evaluation but have limitations.
- Rats offer a larger size and more comprehensive immune system, making them promising for translational studies.
Purpose of the Study:
- To establish an effective method for long-term immune humanization in rats.
- To develop a novel preclinical model for human immunotherapy research.
Main Methods:
- Intrahepatic injection of human CD34+ hematopoietic stem cells into newborn immunodeficient rats expressing human SIRPα.
- Analysis of immune cell populations in blood and lymphoid organs.
- Treatment with anti-human CD3 antibody to assess T cell depletion and cytokine production.
Main Results:
- Successful long-term immune humanization of rats was achieved.
- Human immune system rats exhibited a predominance of T cells followed by B cells in blood, mirroring human immune profiles.
- High levels of immune humanization were observed in central and secondary lymphoid organs.
- Treatment with anti-human CD3 antibody led to T cell depletion and detectable human cytokines in sera.
Conclusions:
- A novel and efficient method for generating human immune system rats has been developed.
- Human immune system rats represent a valuable new model for translational immunology and immunotherapy research.
- This model offers advantages over existing HIS mice, potentially improving the prediction of human responses to therapies.
