Non-Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Human hematopoietic stem cell maintenance and myeloid cell development in next-generation humanized mouse models.

Abstract

Mice repopulated with a human hemato-lymphoid system provide valuable tools for in vivo studies of human hematopoiesis and immunity.1-3 Such humanized mice are generated by transplantation of human CD341 (hCD341) hematopoietic stem and progenitor cells (HSPCs) into preconditioned, immunodeficient mice.4,5 Prkdcscid mutation or Rag deficiency make recipient mice devoid of T and B lymphocytes. They also lack natural killer cells because of inactivation of the Il2rg gene, essential for interleukin-15 (IL-15)–dependent natural killer cell development.6 Mouse-to-human phagocytic tolerance is achieved by expression of the NOD-specific variant of the mouse Sirpa gene or human SIRPA gene, which encode signal regulatory protein a (SIRPa) “don’t eat me” receptors that bind human CD47.7,8 Conventional humanized mouse models (NSG: NOD Scid Il2rg2/29,10; SRG, hSIRPA Rag22/2Il2rg2/28,11) present incomplete replacement of the hemato-lymphoid system and inefficient human myelopoiesis.1 Thus, improved models have recently been developed.