CD34+ Humanized Mouse

Advanced Human Immune System Mouse Models™

The immune system plays a central role in many pathologies such as cancer or inflammatory and autoimmune diseases. Many drug candidates, targeting the immune system, have therefore been developed, revealing the need for predictive pre-clinical models in the field.

TransCure bioServices has developed a highly predictive mouse model with a human immune system. Highly deficient mice are transplanted with CD34+ hematopoietic stem cells from umbilical cord blood. Complete hematopoiesis is fully recapitulated, and 14 weeks after CD34+ engraftment, a fully functional human immune system is established.

Mouse Humanization Process

The main characteristics of this humanized mouse model are:

• Development of a complete and functional human immune system. By comparison to human PBMC engrafted mice, CD34+ humanized mice support the development not only of T cells but also B cells, NK cells, dendritic cells, monocytes and macrophages, allowing testing of many different drug mecanisms of action such as T-cell engagers, ADCC, macrophage polarization…
• All the mouse tissues are infiltrated (peripheral blood, spleen, bone marrow…)
• Poor GvHD onset thanks to high purity of CD34+ hematopoietic cells
• Lifelong stability (>6 months) allowing long term studies
• Highly standardized process: we guarantee a humanization rate above 25% (in average 40% of humanization)
• CD34+ Humanized mice are always in stock. There are no wait times to start your study. We produce over 700 humanized mice every month
• Due to the lack of human cytokines in the system, CD34+ humanized mice are characterized by lower myeloid lineage development and NK cells activity. To overcome this limitation, we have developed the human cytokines boost. Via hydrodynamic gene delivery, we enhance the proliferation and maturation of specific human immune subsets. A cocktail of GM-CSF, IL-3, IL-4 and FLT3L increase the number of monocytes and dendrictic cells. A IL-15 boost increase the number of NK cells and their activity

Myeloid lineage, DC and NK cells Boosting

CD34+ Humanized Mouse FAQ

Below are some frequently asked questions about humanized mice. If you have additional questions please contact us.

1	How do you generate humanized mice?	Humanized mice are generated by engraftment of CD34+ haematopoietic stem cells from human cord blood in immunodeficient mouse strain after a chemoablation treatment. No irradition is performed to avoid anemia and therefore get more robust and stable humanized mice.
2	What type of mouse strain can be humanized?	We can humanize many different mouse strains, all have in common to be highly immunodeficient mouse models: NCG, NOG, NOG-EXL … Our team can guide you on the best model to select based on your Mechanism of Action. Please note that humanized NCG are prepared in advance to speed up the process.
3	What is the advantage of the boost by comparison to transgenic mouse models?	The hydrodynamic boost allows the transient expression of human cytokines, that will support the development and proliferation of immune populations. By comparison to transgenic mouse models that constitutively express human cytokines, no deleterious effects on the mice is observed after the boost. In addition, the hydrodynamic boost technique is fully adaptable.
4	What is the number of mice that can be humanized with one CD34+ cord blood donor?	From one CD34+ human cord blood donor, an average of 20 mice can be humanized. Larger cohorts can be humanized based on specific requests.
5	What type of immune populations subsets can be found in the humanized mice?	All the immune cell subsets are present in the CD34+ humanized mice : T, B, NK, DC, Myeloid, DC, neutrophils, expressing all the markers that you can expect them to express.
6	Is it possible to screen CD34+ donors or use donors with specific haplotypes?	Yes, it is possible, the CD34+ donors could be screened for specific haplotype.
7	Are the human immune cells from CD34+ humanized mice fully functional?	The functionality of the human immune system in CD34+ humanized mice has been demonstrated by the data gathered by TransCure over the last 10 years. Many publications also described the functionality of the human immune cells: T cells can be activated to target tumor cells and elicit and antigen specific T cell response, NK cells , myeloïd cells, Dendritic cells are fully functional.
8	Do the CD34+ humanized mice developped GvHD?	Graft versus host disease is the response of the human immune cells (graft) against the host (mouse) tissues. Thanks to highly purified CD34+ haematopietic stem cells and a well controlled protocol for generation of the humanized mice, by contrast to PBMC engrafted mouse models, the CD34+ humanized mice very rarely develop GvHD. We can keep humanized mice up to one year without GvHD.