Characterization of human engraftment and hemophagocytic lymphohistiocytosis in NSG-SGM3 neonate mice engrafted with purified CD34 + hematopoietic stem cells.

Immunodeficient mice bearing human immune systems, or 'humanized' chimeric mice, are widely used in basic research, along with the preclinical stages of drug development. NOD-SCID IL2Rγnull (NSG) mice expressing human stem cell factor, granulocyte-macrophage colony stimulating factor, and interleukin-3 (NSG-SGM3) support robust development of human myeloid cells and T cells but have reduced longevity due to development of fatal hemophagocytic lymphohistiocytosis (HLH). Here we describe an optimised protocol development of human immune chimerism in NSG-SGM3 mice. We demonstrate that efficient human CD45+ reconstitution can be achieved and HLH delayed by engraftment of neonatal NSG-SGM3 with low numbers of human umbilical cord-derived CD34+ hematopoietic stem cells in the absence of preconditioning irradiation.