Cited by 162Wound Healing and TreatmentsImmune cells in cancerMacrophage Migration Inhibitory Factor

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

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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·2014·PLoS ONE

DOI 10.1371/journal.pone.0102994PMC PMC4113363

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Abstract

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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Authors: Jetten, N., Roumans, N., Gijbels, M. J., Romano, A., Post, M. J., de Winther, M. P. J., van der Hulst, R. R. W. J., & Xanthoulea, S.
Affiliations: Maastricht University (NL)
Maastricht University Medical Centre (NL)
Corresponding author: Xanthoulea, Sofia
ORCID: Roumans, Nadia
Gijbels, Marion J.
Romano, Andrea
Post, Mark J.
Xanthoulea, Sofia
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2014-07-28
Volume: 9
Issue: 7
Pages: e102994
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0102994
PMC: PMC4113363
OpenAlex: W2036736332
Cited by: 162
References: 40
Citations by year: 2026: 5 · 2025: 15 · 2024: 20 · 2023: 16 · 2022: 24 · 2021: 10 · 2020: 13 · 2019: 18 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 4 · 2014: 2
FWCI: 9.68
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Research Publications (Maastricht University) (publishedVersion, cc-by)
Pure Amsterdam UMC (publishedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders: Universiteit Maastricht
Maastricht Universitair Medisch Centrum
Topics: Health Sciences › Medicine › Surgery › Wound Healing and Treatments
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
Keywords: M2 macrophages, macrophage polarization, skin wound healing, diabetic wounds, IL-4, IL-10, re-epithelialization, neutrophils, db/db mice, full-thickness skin wounds
MeSH terms: Animals, Diabetes Mellitus, Experimental, Disease Models, Animal, Female, Immunohistochemistry, Macrophages, Skin, Wound Healing, Gene Expression, Genes, Reporter, Mice

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

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