title: Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors.
abstract: Better methods to characterize normal human hematopoietic cells with short-term repopulating activity cells (STRCs) are needed to facilitate improving recovery rates in transplanted patients.We now show that 5-fold more human myeloid cells are produced in sublethally irradiated NOD/SCID-IL-2Receptor-γchain-null (NSG) mice engineered to constitutively produce human interleukin-3, granulocyte-macrophage colony-stimulating factor and Steel factor (NSG-3GS mice) than in regular NSG mice 3 weeks after an intravenous injection of CD34 human cord blood cells. Importantly, the NSG-3GS mice also show a concomitant and matched increase in circulating mature human neutrophils. Imaging NSG-3GS recipients of lenti-luciferase-transduced cells showed that human cells being produced 3 weeks posttransplant were heterogeneously distributed, validating the blood as a more representative measure of transplanted STRC activity. Limiting dilution transplants further demonstrated that the early increase in human granulopoiesis in NSG-3GS mice reflects an expanded output of differentiated cells per STRC rather than an increase in STRC detection.
  
  
  CONCLUSIONS
  NSG-3GS mice support enhanced clonal outputs from human short-term repopulating cells (STRCs) without affecting their engrafting efficiency. Increased human STRC clone sizes enable their more precise and efficient measurement by peripheral blood monitoring.
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Miller
authors.forename: Alice M S
authors.initials: AM
authors.lastname: Cheung
authors.forename: Philip A
authors.initials: PA
authors.lastname: Beer
authors.forename: David J H F
authors.initials: DJ
authors.lastname: Knapp
authors.forename: Kiran
authors.initials: K
authors.lastname: Dhillon
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rabu
authors.forename: Shabnam
authors.initials: S
authors.lastname: Rostamirad
authors.forename: R Keith
authors.initials: RK
authors.lastname: Humphries
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
mesh_terms: D000818:Animals; D036101:Cord Blood Stem Cell Transplantation; D006085:Graft Survival; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D038042:Myelopoiesis; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: C508596:IL3 protein, human; D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor