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- Title
Characterization of M1 and M2 polarization of macrophages in vascularized human dermo-epidermal skin substitutes in vivo.
- Authors
Klar, Agnes S.; Michalak-Mićka, Katarzyna; Biedermann, Thomas; Simmen-Meuli, Claudia; Reichmann, Ernst; Meuli, Martin
- Abstract
<bold>Aims and Objectives: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
MACROPHAGES; SKIN physiology; TISSUE engineering; TREATMENT for burns &; scalds; MESENCHYMAL stem cells; ADIPOSE tissues; PROTEIN metabolism; ANIMAL experimentation; BIOLOGICAL models; CELL culture; CELL receptors; CONNECTIVE tissue cells; DERMIS; EPIDERMIS; KERATINOCYTES; OXIDOREDUCTASES; RATS; SKIN grafting; WOUND healing; PHENOTYPES; ARTIFICIAL skin
- Publication
Pediatric Surgery International, 2018, Vol 34, Issue 2, p129
- ISSN
0179-0358
- Publication type
journal article
- DOI
10.1007/s00383-017-4179-z