F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo
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...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/2414906 |
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| _version_ | 1832563798984097792 |
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| author | Heather L. Thompson Nico van Rooijen Bryce T. McLelland Jennifer O. Manilay |
| author_facet | Heather L. Thompson Nico van Rooijen Bryce T. McLelland Jennifer O. Manilay |
| author_sort | Heather L. Thompson |
| collection | DOAJ |
| description | 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 ESHPs in 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 vivo depletion 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 targets in vitro. Taken together, these results suggest that macrophages are a barrier to both syngeneic and allogeneic ESHP engraftment in vivo. |
| format | Article |
| id | doaj-art-b3fcfe1a78de4165bcb7ae5ed7457007 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-b3fcfe1a78de4165bcb7ae5ed74570072025-02-03T01:12:33ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/24149062414906F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In VivoHeather L. Thompson0Nico van Rooijen1Bryce T. McLelland2Jennifer O. Manilay3Quantitative and Systems Biology Graduate Group, School of Natural Sciences, University of California-Merced, Merced, CA 95340, USADepartment of Molecular Cell Biology, Vrije University, Amsterdam, NetherlandsQuantitative and Systems Biology Graduate Group, School of Natural Sciences, University of California-Merced, Merced, CA 95340, USAQuantitative and Systems Biology Graduate Group, School of Natural Sciences, University of California-Merced, Merced, CA 95340, USAUnderstanding 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 ESHPs in 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 vivo depletion 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 targets in vitro. Taken together, these results suggest that macrophages are a barrier to both syngeneic and allogeneic ESHP engraftment in vivo.http://dx.doi.org/10.1155/2016/2414906 |
| spellingShingle | Heather L. Thompson Nico van Rooijen Bryce T. McLelland Jennifer O. Manilay F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo Journal of Immunology Research |
| title | F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo |
| title_full | F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo |
| title_fullStr | F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo |
| title_full_unstemmed | F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo |
| title_short | F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo |
| title_sort | f4 80 host macrophages are a barrier to murine embryonic stem cell derived hematopoietic progenitor engraftment in vivo |
| url | http://dx.doi.org/10.1155/2016/2414906 |
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