Characterization of M1 and M2 polarization of macrophages in vascularized human dermo-epidermal skin substitutes in vivo.
Pediatr Surg Int
; 34(2): 129-135, 2018 Feb.
Article
em En
| MEDLINE
| ID: mdl-29124400
ABSTRACT
AIMS AND OBJECTIVES:
Vascularized bio-engineered human dermo-epidermal skin substitutes (vascDESS) hold promise for treating burn patients, including those with severe full-thickness wounds. We have previously shown that vascDESS promote wound healing by enhanced influx of macrophages and granulocytes. Immediately following transplantation, macrophages infiltrate the graft and differentiate into a pro-inflammatory (M1) or a pro-healing M2 phenotype. The aim of this study was to characterize the activation state of macrophages infiltrating skin transplants at distinct time points following transplantation.METHODS:
Keratinocytes and the stromal vascular fraction (SVF) were derived from human skin or adipose tissue, respectively. Human SVF containing both endothelial and mesenchymal/stromal cells was used to generate vascularized dermal component in vitro, which was subsequently covered with human keratinocytes. Finally, vascDESS were transplanted on the back of immuno-incompetent rats, excised, and analyzed after 1 and 3 weeks using immunohistological techniques.RESULTS:
A panel of markers of macrophage M1 (nitric oxide synthase iNOS) and M2 (CD206) subclass was used. All skin grafts were infiltrated by both M1 and M2 rat macrophages between 1-3 weeks post-transplantation. CD68 (PG-M1) was used as a pan-macrophage marker. The number of CD68+CD206+ M2-polarized macrophages was higher in 3-week transplants as compared to early-stage transplants (1 week). In contrast, the number of CD68+iNOS+ M1 cells was markedly decreased in later stages in vivo.CONCLUSIONS:
Macrophages exhibit a heterogeneous and temporally regulated polarization during skin wound healing. Our results suggest that the phenotype of macrophages changes during healing from a more pro-inflammatory (M1) profile in early stages after injury, to a less inflammatory, pro-healing (M2) phenotype in later phases in vivo.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Queratinócitos
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Tecido Adiposo
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Transplante de Pele
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Derme
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Engenharia Tecidual
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Células Epidérmicas
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Macrófagos
Limite:
Adolescent
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Animals
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Child
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Child, preschool
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Humans
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Infant
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Male
Idioma:
En
Revista:
Pediatr Surg Int
Ano de publicação:
2018
Tipo de documento:
Article