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Cellular and microenvironmental cues that promote macrophage fusion and foreign body response

Stewart, Chloe L.; Marlow, Maria; Zelzer, Mischa; Hook, Andrew L.; Piccinini, Anna M.

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Authors

Chloe L. Stewart

ANDREW HOOK ANDREW.HOOK@NOTTINGHAM.AC.UK
Assistant Professor



Abstract

During the foreign body response (FBR), macrophages fuse to form foreign body giant cells (FBGCs). Modulation of FBGC formation can prevent biomaterial degradation and loss of therapeutic efficacy. However, the microenvironmental cues that dictate FBGC formation are poorly understood with conflicting reports. Here, we identified molecular and cellular factors involved in driving FBGC formation in vitro. Macrophages demonstrated distinct fusion competencies dependent on monocyte differentiation. The transition from a proinflammatory to a reparative microenvironment, characterised by specific cytokine and growth factor programmes, accompanied FBGC formation. Toll-like receptor signalling licensed the formation of FBGCs containing more than 10 nuclei but was not essential for cell-cell fusion to occur. Moreover, the fibroblastmacrophage crosstalk influenced FBGC development, with the fibroblast secretome inducing macrophages to secrete more PDGF, which enhanced large FBGC formation. These findings advance our understanding as to how a specific and timely combination of cellular and microenvironmental factors is required for an effective FBR, with monocyte differentiation and fibroblasts being key players.

Journal Article Type Article
Acceptance Date Jun 13, 2024
Online Publication Date Jul 5, 2024
Deposit Date Jun 14, 2024
Publicly Available Date Jun 28, 2024
Journal Frontiers in Immunology
Electronic ISSN 1664-3224
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 15
DOI https://doi.org/10.3389/fimmu.2024.1411872
Keywords macrophage, macrophage fusion, foreign body response, foreign body giant cell,10 Toll-like receptor signalling, fibroblast
Public URL https://nottingham-repository.worktribe.com/output/36014838
Publisher URL https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1411872/abstract

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