title: F4/80+Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor EngraftmentIn Vivo.
abstract: Understanding how embryonic stem cells and their derivatives interact with the adult host immune system is critical to developing their therapeutic potential. Murine embryonic stem cell-derived hematopoietic progenitors (ESHPs) were generated via coculture with the bone marrow stromal cell line, OP9, and then transplanted into NOD.SCID.Common Gamma Chain (NSG) knockout mice, which lack B, T, and natural killer cells. Compared to control mice transplanted with adult lineage-negative bone marrow (Lin-BM) progenitors, ESHP-transplanted mice attained a low but significant level of donor hematopoietic chimerism. Based on our previous studies, we hypothesized that macrophages might contribute to the low engraftment of ESHPsin vivo. Enlarged spleens were observed in ESHP-transplanted mice and found to contain higher numbers of host F4/80+macrophages compared to BM-transplanted controls.In vivodepletion of host macrophages using clodronate-loaded liposomes improved the ESHP-derived hematopoietic chimerism in the spleen but not in the BM. F4/80+macrophages demonstrated a striking propensity to phagocytose ESHP targetsin vitro. Taken together, these results suggest that macrophages are a barrier to both syngeneic and allogeneic ESHP engraftmentin vivo.
authors.affiliation: Quantitative and Systems Biology Graduate Group, School of Natural Sciences, University of California-Merced, Merced, CA 95340, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Thompson
authors.affiliation: Department of Molecular Cell Biology, Vrije University, Amsterdam, Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.affiliation: Quantitative and Systems Biology Graduate Group, School of Natural Sciences, University of California-Merced, Merced, CA 95340, USA.
authors.forename: Bryce T
authors.initials: BT
authors.lastname: McLelland
authors.affiliation: Quantitative and Systems Biology Graduate Group, School of Natural Sciences, University of California-Merced, Merced, CA 95340, USA; Molecular and Cell Biology Unit, School of Natural Sciences, University of California-Merced, Merced, CA 95340, USA.
authors.forename: Jennifer O
authors.identifier: 0000-0002-1431-5295
authors.initials: JO
authors.lastname: Manilay
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology*; D006085:Graft Survival / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis / Q000276:immunology; D018183:Transplantation Chimera; D014181:Transplantation Immunology
chemical_list: D000954:Antigens, Surface