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 CD34+ (hCD34+) 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 α (SIRPα) “don’t eat meÁ receptors that bind human CD47.7,8 Conventional humanized mouse models (NSG: NOD Scid Il2rg−/−9,10; SRG, hSIRPA Rag2−/−Il2rg−/−8,11) present incomplete replacement of the hemato-lymphoid system and inefficient human myelopoiesis.1 Thus, improved models have recently been developed. We have compared human HSPC maintenance and myelopoiesis in 3 of the newer models: NSG-SGM3 (also designated NSGS), NSGW41, and MISTRG.