The natural behavior of mononuclear phagocytes in HTS formation.

Hypertrophic scars (HTS) are caused by trauma or burn injuries to the deep dermis and are considered fibrosis in the skin. Monocytes, M1 and M2 macrophages are mononuclear phagocytes. Studies suggest that M2 macrophages are profibrotic and might contribute to HTS formation. Our lab has established a...

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Publicado en:Wound Repair & Regeneration Vol. 24; no. 1; pp. 14 - 26
Autores principales: Zhu, Zhensen, Ding, Jie, Ma, Zengshuan, Iwashina, Takashi, Tredget, Edward E
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell Jan/Feb2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jan/Feb2016
      vid: 24
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        atl: The natural behavior of mononuclear phagocytes in HTS formation.
      aug:
        au:
          Zhu, Zhensen
          Ding, Jie
          Ma, Zengshuan
          Iwashina, Takashi
          Tredget, Edward E
        affil: Division of Plastic and Reconstructive Surgery, Wound Healing Research Group, University of Alberta, Edmonton, Alberta, Canada
      sug:
        subj:
          Phagocytes Physiology
          Skin Pathology
          Fibrosis
          Funding Source
          Models, Biological
          Animal Studies
          In Vivo Studies
          Mice
          Human
          Skin Transplantation
          Histological Techniques
          Collagen Analysis
          Fibroblasts Analysis
          Macrophages Analysis
          Monocytes Analysis
          Xenografts
          Phenotype Evaluation
          Cicatrix, Hypertrophic
          Female
          Digital Imaging
          Staining and Labeling
          Immunochemistry
          Flow Cytometry
          Reverse Transcriptase Polymerase Chain Reaction
          Descriptive Statistics
          Data Analysis Software
          Two-Tailed Test
          Unpaired T-Tests
          One-Way Analysis of Variance
          Post Hoc Analysis
          P-Value
          Female
      ab: Hypertrophic scars (HTS) are caused by trauma or burn injuries to the deep dermis and are considered fibrosis in the skin. Monocytes, M1 and M2 macrophages are mononuclear phagocytes. Studies suggest that M2 macrophages are profibrotic and might contribute to HTS formation. Our lab has established a human HTS-like nude mouse model, in which the grafted human skin develops red, raised, and firm scarring, resembling HTS seen in humans. In this study, we observed the natural behavior of mononuclear phagocyte system in this nude mouse model of dermal fibrosis at multiple time points. Thirty athymic nude mice received human skin grafts and an equal number of mice received mouse skin grafts as controls. The grafted skin and blood were harvested at 1, 2, 3, 4, and 8 weeks. Wound area, thickness, collagen morphology and level, the cell number of myofibroblasts, M1- and M2-like macrophages in the grafted skin, as well as monocyte fraction in the blood were investigated at each time points. Xenografted mice developed contracted and thickened scars grossly. The xenografted skin resembled human HTS tissue based on enhanced thickness, fibrotic orientation of collagen bundles, increased collagen level, and infiltration of myofibroblasts. In the blood, monocytes dramatically decreased at 1 week postgrafting and gradually returned to normal in the following 8 weeks. In the xenografted skin, M1-like macrophages were found predominantly at 1-2 weeks postgrafting; whereas, M2-like macrophages were abundant at later time points, 3-4 weeks postgrafting coincident with the development of fibrosis in the human skin tissues. This understanding of the natural behavior of mononuclear phagocytes in vivo in our mouse model provides evidence for the role of M2- like macrophages in fibrosis of human skin and suggests that macrophage depletion in the subacute phases of wound healing might reduce or prevent HTS formation.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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