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Macrophage contribution to the survival of transferred expanded skin flap through angiogenesis
BACKGROUND: Despite the application of tissue expansion in the reconstruction of significant tissue defects, complications with expanded random-pattern skin flaps remain a major challenge. Insufficient angiogenesis is one of the keys factors in flap ischemia and dysfunction. Macrophages play a key r...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113100/ https://www.ncbi.nlm.nih.gov/pubmed/37082668 http://dx.doi.org/10.21037/atm-22-1558 |
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author | Huang, Zhaosong Ding, Jianke Song, Yajuan Liu, Wei Dong, Chen Zhang, Yu Wang, Tong Du, Jing Xiong, Shaoheng He, Qiang Yu, Zhou Ma, Xianjie |
author_facet | Huang, Zhaosong Ding, Jianke Song, Yajuan Liu, Wei Dong, Chen Zhang, Yu Wang, Tong Du, Jing Xiong, Shaoheng He, Qiang Yu, Zhou Ma, Xianjie |
author_sort | Huang, Zhaosong |
collection | PubMed |
description | BACKGROUND: Despite the application of tissue expansion in the reconstruction of significant tissue defects, complications with expanded random-pattern skin flaps remain a major challenge. Insufficient angiogenesis is one of the keys factors in flap ischemia and dysfunction. Macrophages play a key role in promoting tissue angiogenesis, but their effects on expanded flap angiogenesis and the survival of the transferred skin flap are still unknown. METHODS: A rat scalp expansion model was established to evaluate the dynamic changes of macrophages in expanded skin. Clodronate liposomes (Clo-lipo) were injected into the expanded scalps to deplete the macrophages, and the expanded scalp flaps with macrophage depletion were orthotopically transferred. The remaining expanded rat scalp flaps were treated with either a macrophage-colony stimulating factor (M-CSF) alone or M-CSF in combination with Clo-lipo and transferred. The number of macrophages, blood perfusion, microvascular densities (MVDs), flap survival, histological changes, and gene expression related to macrophage polarization and angiogenesis were determined with immunofluorescence (IF) staining, full-field laser perfusion imager, hematoxylin and eosin (HE) staining, and quantitative real-time polymerase chain reaction. RESULTS: The number of pan-macrophages significantly increased in the expanded scalp on days 14 and 21 after expander placement. The depletion rate after treatment with Clo-lipo was 29.06%, and the number of macrophages was significantly reduced in the group that underwent Clo-lipo treatment on day 14 before flap transfer (P<0.05). Macrophage depletion resulted in decreased blood perfusion, reduced MVDs, lower expression of factors, and poor survival rate. The recruitment of macrophages with a M-CSF led to higher blood perfusion, increased MVDs, greater expression of angiogenic factors, and better flap survival after flap transfer. CONCLUSIONS: Alternatively activated macrophages in the expanded flap could significantly promote angiogenesis, improve blood perfusion, and ultimately increase the flap survival rate. Modulating alternatively activated macrophages may provide a key therapeutic strategy to promote expanded skin flap survival. Our study has provided a basis for clinically improving random-pattern skin flap survival. |
format | Online Article Text |
id | pubmed-10113100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-101131002023-04-19 Macrophage contribution to the survival of transferred expanded skin flap through angiogenesis Huang, Zhaosong Ding, Jianke Song, Yajuan Liu, Wei Dong, Chen Zhang, Yu Wang, Tong Du, Jing Xiong, Shaoheng He, Qiang Yu, Zhou Ma, Xianjie Ann Transl Med Original Article BACKGROUND: Despite the application of tissue expansion in the reconstruction of significant tissue defects, complications with expanded random-pattern skin flaps remain a major challenge. Insufficient angiogenesis is one of the keys factors in flap ischemia and dysfunction. Macrophages play a key role in promoting tissue angiogenesis, but their effects on expanded flap angiogenesis and the survival of the transferred skin flap are still unknown. METHODS: A rat scalp expansion model was established to evaluate the dynamic changes of macrophages in expanded skin. Clodronate liposomes (Clo-lipo) were injected into the expanded scalps to deplete the macrophages, and the expanded scalp flaps with macrophage depletion were orthotopically transferred. The remaining expanded rat scalp flaps were treated with either a macrophage-colony stimulating factor (M-CSF) alone or M-CSF in combination with Clo-lipo and transferred. The number of macrophages, blood perfusion, microvascular densities (MVDs), flap survival, histological changes, and gene expression related to macrophage polarization and angiogenesis were determined with immunofluorescence (IF) staining, full-field laser perfusion imager, hematoxylin and eosin (HE) staining, and quantitative real-time polymerase chain reaction. RESULTS: The number of pan-macrophages significantly increased in the expanded scalp on days 14 and 21 after expander placement. The depletion rate after treatment with Clo-lipo was 29.06%, and the number of macrophages was significantly reduced in the group that underwent Clo-lipo treatment on day 14 before flap transfer (P<0.05). Macrophage depletion resulted in decreased blood perfusion, reduced MVDs, lower expression of factors, and poor survival rate. The recruitment of macrophages with a M-CSF led to higher blood perfusion, increased MVDs, greater expression of angiogenic factors, and better flap survival after flap transfer. CONCLUSIONS: Alternatively activated macrophages in the expanded flap could significantly promote angiogenesis, improve blood perfusion, and ultimately increase the flap survival rate. Modulating alternatively activated macrophages may provide a key therapeutic strategy to promote expanded skin flap survival. Our study has provided a basis for clinically improving random-pattern skin flap survival. AME Publishing Company 2023-01-30 2023-03-31 /pmc/articles/PMC10113100/ /pubmed/37082668 http://dx.doi.org/10.21037/atm-22-1558 Text en 2023 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Huang, Zhaosong Ding, Jianke Song, Yajuan Liu, Wei Dong, Chen Zhang, Yu Wang, Tong Du, Jing Xiong, Shaoheng He, Qiang Yu, Zhou Ma, Xianjie Macrophage contribution to the survival of transferred expanded skin flap through angiogenesis |
title | Macrophage contribution to the survival of transferred expanded skin flap through angiogenesis |
title_full | Macrophage contribution to the survival of transferred expanded skin flap through angiogenesis |
title_fullStr | Macrophage contribution to the survival of transferred expanded skin flap through angiogenesis |
title_full_unstemmed | Macrophage contribution to the survival of transferred expanded skin flap through angiogenesis |
title_short | Macrophage contribution to the survival of transferred expanded skin flap through angiogenesis |
title_sort | macrophage contribution to the survival of transferred expanded skin flap through angiogenesis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113100/ https://www.ncbi.nlm.nih.gov/pubmed/37082668 http://dx.doi.org/10.21037/atm-22-1558 |
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