Mice Description

Human HSC (hematopoietic stem cells ) engrafted humanized mice are a powerful model allows researchers to examine the human immune system and related primates‘ alien virus research and cellular immunotherapy preclinical evaluation. However, maintenance, differentiation, and function of human hematopoietic cells are suboptimal in these hosts. Thrombopoietin (THPO) has been demonstrated as a crucial cytokine supporting maintenance and self-renewal of HSCs. Moreover, a species barrier between human immune cells and the mouse microenvironment limits human acquired as well as innate immune cell development. Such as frequencies of human macrophages cells did not reach physiological levels in B-NDG humanized mice. Cytokines CSF1 has been reported controls the production, differentiation, and function of monocytes and macrophages cells.

Biocytogen developed the B-NDG hCSF1/hTHPO mice in which we replaced the gene encoding mouseCsf1/Thpoby its human CDS region. This mouse combines a B-NDG mouse background and expresses human hCSF1/hTHPO protein, will become a suitable animal model to investigate development and function of human macrophage cells without irradiation treatment.

Background

Genomic organization and expression of theThpogene

Activation of the TPO receptor by TPO or TPO receptor agonists. TPO and romiplostim bind to the distal cytokine receptor homology domain (CRH-2) of the preformed, inactive TPO receptor dimer. Eltrombopag binds to the transmembrane region of the TPO receptor. Multiple signal transduction pathways are thereby activated.

Kuter, D. J. The biology of thrombopoietin and thrombopoietin receptor agonists. International journal of hematology 98, 10-23, doi:10.1007/s12185-013-1382-0 (2013).

CSF-1 regulation of the wandering macrophage

Circulating CSF-1, produced by endothelial cells in blood vessels, together with locally produced CSF-1 regulates the survival, proliferation and differentiation of mononuclear phagocytes and osteoclasts.

CSF-1 regulation of the wandering macrophage: complexity in action Fiona J. Pixley and E. Richard Stanley, 2004

HSC Human Immune System Engraftment

Human CD34+ cells (0.15 M) were intravenously injected into homozygote B-NDG hCSF1/hTHPO mice (female, 6 week-old, n=15). Representative flow cytometric analysis of peripheral blood lymphocyte from mice after engraftment with human CD34+ cells. human multi-lineage cells, including T, B, NK, myeloid cells，monocyte and neutrophils, were successfully constructed. Our results suggest that the human HSC (hematopoietic stem cells) engrafted humanized mice model was successfully constructed.