Cellular and microenvironmental cues that promote macrophage fusion and foreign body response
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 conflictin...
| Главные авторы: | , , , , |
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| Формат: | Journal article |
| Язык: | English |
| Опубликовано: |
Frontiers Media
2024
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| _version_ | 1826313545304768512 |
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| author | Stewart, CL Hook, AL Zelzer, M Marlow, M Piccinini, AM |
| author_facet | Stewart, CL Hook, AL Zelzer, M Marlow, M Piccinini, AM |
| author_sort | Stewart, CL |
| collection | OXFORD |
| description | 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 fibroblast-macrophage 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. |
| first_indexed | 2024-09-25T04:16:21Z |
| format | Journal article |
| id | oxford-uuid:fb9d1357-c998-43bd-8e71-f8dbef83df26 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:16:21Z |
| publishDate | 2024 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:fb9d1357-c998-43bd-8e71-f8dbef83df262024-07-19T20:07:26ZCellular and microenvironmental cues that promote macrophage fusion and foreign body responseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fb9d1357-c998-43bd-8e71-f8dbef83df26EnglishJisc Publications RouterFrontiers Media2024Stewart, CLHook, ALZelzer, MMarlow, MPiccinini, AMDuring 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 fibroblast-macrophage 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. |
| spellingShingle | Stewart, CL Hook, AL Zelzer, M Marlow, M Piccinini, AM Cellular and microenvironmental cues that promote macrophage fusion and foreign body response |
| title | Cellular and microenvironmental cues that promote macrophage fusion and foreign body response |
| title_full | Cellular and microenvironmental cues that promote macrophage fusion and foreign body response |
| title_fullStr | Cellular and microenvironmental cues that promote macrophage fusion and foreign body response |
| title_full_unstemmed | Cellular and microenvironmental cues that promote macrophage fusion and foreign body response |
| title_short | Cellular and microenvironmental cues that promote macrophage fusion and foreign body response |
| title_sort | cellular and microenvironmental cues that promote macrophage fusion and foreign body response |
| work_keys_str_mv | AT stewartcl cellularandmicroenvironmentalcuesthatpromotemacrophagefusionandforeignbodyresponse AT hookal cellularandmicroenvironmentalcuesthatpromotemacrophagefusionandforeignbodyresponse AT zelzerm cellularandmicroenvironmentalcuesthatpromotemacrophagefusionandforeignbodyresponse AT marlowm cellularandmicroenvironmentalcuesthatpromotemacrophagefusionandforeignbodyresponse AT piccininiam cellularandmicroenvironmentalcuesthatpromotemacrophagefusionandforeignbodyresponse |