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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 me” 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.

Authors: Sippel TR, Radtke S, Olsen TM, Kiem HP, Rongvaux A.
Journal: Blood Adv. 2019 Feb 12;3(3):268-274
Year: 2019
PubMed: Find in PubMed