title: Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain.
abstract: Poor myeloid engraftment remains a barrier to experimental use of humanized mice. Focusing primarily on peripheral blood cells, we compared the engraftment profile of NOD-scid-IL2Rγc(-/-) (NSG) mice with that of NSG mice transgenic for human membrane stem cell factor (hu-mSCF mice), NSG mice transgenic for human interleukin (IL)-3, granulocyte-macrophage-colony stimulating factor (GM-CSF), and stem cell factor (SGM3 mice). hu-mSCF and SGM3 mice showed enhanced engraftment of human leukocytes compared to NSG mice, and this was reflected in the number of human neutrophils and monocytes present in these strains. Importantly, discrete classical, intermediate, and nonclassical monocyte populations were identifiable in the blood of NSG and hu-mSCF mice, while the nonclassical population was absent in the blood of SGM3 mice. Granulocyte-colony stimulating factor (GCSF) treatment increased the number of blood monocytes in NSG and hu-mSCF mice, and neutrophils in NSG and SGM3 mice; however, this effect appeared to be at least partially dependent on the stem cell donor used to engraft the mice. Furthermore, GCSF treatment resulted in a preferential expansion of nonclassical monocytes in both NSG and hu-mSCF mice. Human tubulointerstitial CD11c(+) cells were present in the kidneys of hu-mSCF mice, while monocytes and neutrophils were identified in the liver of all strains. Bone marrow-derived macrophages prepared from NSG mice were most effective at phagocytosing polystyrene beads. In conclusion, hu-mSCF mice provide the best environment for the generation of human myeloid cells, with GCSF treatment further enhancing peripheral blood human monocyte cell numbers in this strain.
authors.affiliation: 1 Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin , Dublin, Ireland .
authors.forename: Alice M
authors.initials: AM
authors.lastname: Coughlan
authors.affiliation: 2 Comparative Immunology, School of Biochemistry and Immunology, Trinity College Dublin , Dublin, Ireland .
authors.forename: Cathal
authors.initials: C
authors.lastname: Harmon
authors.affiliation: 2 Comparative Immunology, School of Biochemistry and Immunology, Trinity College Dublin , Dublin, Ireland .
authors.forename: Sarah
authors.initials: S
authors.lastname: Whelan
authors.affiliation: 1 Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin , Dublin, Ireland .
authors.forename: Eóin C
authors.initials: EC
authors.lastname: O'Brien
authors.affiliation: 1 Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin , Dublin, Ireland .
authors.forename: Vincent P
authors.initials: VP
authors.lastname: O'Reilly
authors.affiliation: 3 Department of Pathology, the Adelaide and Meath Hospital , Dublin, Ireland .
authors.forename: Paul
authors.initials: P
authors.lastname: Crotty
authors.affiliation: 4 School of Veterinary Medicine, University College Dublin , Dublin, Ireland .
authors.forename: Pamela
authors.initials: P
authors.lastname: Kelly
authors.affiliation: 1 Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin , Dublin, Ireland .
authors.forename: Michelle
authors.initials: M
authors.lastname: Ryan
authors.affiliation: 1 Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin , Dublin, Ireland .
authors.forename: Fionnuala B
authors.initials: FB
authors.lastname: Hickey
authors.affiliation: 2 Comparative Immunology, School of Biochemistry and Immunology, Trinity College Dublin , Dublin, Ireland .
authors.forename: Cliona
authors.initials: C
authors.lastname: O'Farrelly
authors.affiliation: 1 Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin , Dublin, Ireland .
authors.forename: Mark A
authors.initials: MA
authors.lastname: Little
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D016688:Mice, Inbred NOD; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D009504:Neutrophils / Q000166:cytology; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
chemical_list: D007377:Interleukin-3; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor