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Journal of Immunology Research
Volume 2016, Article ID 2414906, 12 pages
http://dx.doi.org/10.1155/2016/2414906
Research Article

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

1Quantitative and Systems Biology Graduate Group, School of Natural Sciences, University of California-Merced, Merced, CA 95340, USA
2Department of Molecular Cell Biology, Vrije University, Amsterdam, Netherlands
3Molecular and Cell Biology Unit, School of Natural Sciences, University of California-Merced, Merced, CA 95340, USA

Received 22 May 2016; Revised 3 September 2016; Accepted 4 October 2016

Academic Editor: Xiao-Feng Yang

Copyright © 2016 Heather L. Thompson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.