F4/80(+) Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo

Heather L Thompson, Nico van Rooijen, Bryce T McLelland, Jennifer O Manilay

Research output: Contribution to journalArticleAcademicpeer-review

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 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.

Original languageEnglish
Pages (from-to)2414906
JournalJournal of Immunology Research
Volume2016
DOIs
Publication statusPublished - 2016

Cite this

Thompson, Heather L ; van Rooijen, Nico ; McLelland, Bryce T ; Manilay, Jennifer O. / F4/80(+) Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo. In: Journal of Immunology Research. 2016 ; Vol. 2016. pp. 2414906.
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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 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.",
keywords = "Animals, Antigens, Surface, Embryonic Stem Cells, Graft Survival, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Immunophenotyping, Macrophages, Mice, Phagocytosis, Transplantation Chimera, Transplantation Immunology, Journal Article",
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F4/80(+) Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo. / Thompson, Heather L; van Rooijen, Nico; McLelland, Bryce T; Manilay, Jennifer O.

In: Journal of Immunology Research, Vol. 2016, 2016, p. 2414906.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - F4/80(+) Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo

AU - Thompson, Heather L

AU - van Rooijen, Nico

AU - McLelland, Bryce T

AU - Manilay, Jennifer O

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AB - 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.

KW - Animals

KW - Antigens, Surface

KW - Embryonic Stem Cells

KW - Graft Survival

KW - Hematopoietic Stem Cell Transplantation

KW - Hematopoietic Stem Cells

KW - Immunophenotyping

KW - Macrophages

KW - Mice

KW - Phagocytosis

KW - Transplantation Chimera

KW - Transplantation Immunology

KW - Journal Article

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SN - 2314-8861

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