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Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses

Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profi...

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Autores principales: Jetten, Nadine, Roumans, Nadia, Gijbels, Marion J., Romano, Andrea, Post, Mark J., de Winther, Menno P. J., van der Hulst, Rene R. W. J., Xanthoulea, Sofia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113363/
https://www.ncbi.nlm.nih.gov/pubmed/25068282
http://dx.doi.org/10.1371/journal.pone.0102994
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author Jetten, Nadine
Roumans, Nadia
Gijbels, Marion J.
Romano, Andrea
Post, Mark J.
de Winther, Menno P. J.
van der Hulst, Rene R. W. J.
Xanthoulea, Sofia
author_facet Jetten, Nadine
Roumans, Nadia
Gijbels, Marion J.
Romano, Andrea
Post, Mark J.
de Winther, Menno P. J.
van der Hulst, Rene R. W. J.
Xanthoulea, Sofia
author_sort Jetten, Nadine
collection PubMed
description Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macrophages to promote wound healing in an experimental mouse model of cutaneous injury. Bone marrow derived macrophages were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2-polarized cells, M2a or M2c respectively. Polarized macrophages were injected into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db mice. Control groups were injected with non-polarized (M0) macrophages or saline. Our data indicate that despite M2 macrophages exhibit an anti-inflammatory phenotype in-vitro, they do not improve wound closure in wild type mice while they delay healing in diabetic mice. Examination of wounds on day 15 post-injury indicated delayed re-epithelialization and persistence of neutrophils in M2 macrophage treated diabetic wounds. Therefore, topical application of ex-vivo generated M2 macrophages is not beneficial and contraindicated for cell therapy of skin wounds.
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spelling pubmed-41133632014-08-04 Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses Jetten, Nadine Roumans, Nadia Gijbels, Marion J. Romano, Andrea Post, Mark J. de Winther, Menno P. J. van der Hulst, Rene R. W. J. Xanthoulea, Sofia PLoS One Research Article Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macrophages to promote wound healing in an experimental mouse model of cutaneous injury. Bone marrow derived macrophages were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2-polarized cells, M2a or M2c respectively. Polarized macrophages were injected into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db mice. Control groups were injected with non-polarized (M0) macrophages or saline. Our data indicate that despite M2 macrophages exhibit an anti-inflammatory phenotype in-vitro, they do not improve wound closure in wild type mice while they delay healing in diabetic mice. Examination of wounds on day 15 post-injury indicated delayed re-epithelialization and persistence of neutrophils in M2 macrophage treated diabetic wounds. Therefore, topical application of ex-vivo generated M2 macrophages is not beneficial and contraindicated for cell therapy of skin wounds. Public Library of Science 2014-07-28 /pmc/articles/PMC4113363/ /pubmed/25068282 http://dx.doi.org/10.1371/journal.pone.0102994 Text en © 2014 Jetten et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jetten, Nadine
Roumans, Nadia
Gijbels, Marion J.
Romano, Andrea
Post, Mark J.
de Winther, Menno P. J.
van der Hulst, Rene R. W. J.
Xanthoulea, Sofia
Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses
title Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses
title_full Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses
title_fullStr Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses
title_full_unstemmed Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses
title_short Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses
title_sort wound administration of m2-polarized macrophages does not improve murine cutaneous healing responses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113363/
https://www.ncbi.nlm.nih.gov/pubmed/25068282
http://dx.doi.org/10.1371/journal.pone.0102994
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