Evolution of ischemia and neovascularization in a murine model of full thickness human wound healing.

Translation of wound healing research is limited by the lack of an appropriate animal model, due to the anatomic and wound healing differences in animals and humans. Here, we characterize healing of grafted, full‐thickness human skin in an in vivo model of wound healing. Full‐thickness human skin, o...

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Publicado en:Wound Repair & Regeneration Vol. 28; no. 6; pp. 812 - 823
Autores principales: Karim, Aos S., Liu, Aiping, Lin, Christie, Uselmann, Adam J., Eliceiri, Kevin W., Brown, Matthew E., Gibson, Angela L. F.
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell Nov2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Nov2020
      vid: 28
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1111/wrr.12847
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        atl: Evolution of ischemia and neovascularization in a murine model of full thickness human wound healing.
      aug:
        au:
          Karim, Aos S.
          Liu, Aiping
          Lin, Christie
          Uselmann, Adam J.
          Eliceiri, Kevin W.
          Brown, Matthew E.
          Gibson, Angela L. F.
        affil: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison Wisconsin, USA
      sug:
        subj:
          Ischemia
          Neovascularization, Physiologic
          Wound Healing Physiology
          Xenografts
          Animal Studies
          Mice
          Models, Biological
          In Vivo Studies
          Anoxia
      ab: Translation of wound healing research is limited by the lack of an appropriate animal model, due to the anatomic and wound healing differences in animals and humans. Here, we characterize healing of grafted, full‐thickness human skin in an in vivo model of wound healing. Full‐thickness human skin, obtained from reconstructive operations, was grafted onto the dorsal flank of NOD.Cg‐KitW41JTyr + PrkdcscidIl2rgtm1Wjl/ThomJ mice. The xenografts were harvested 1 to 12 weeks after grafting, and histologic analyses were completed for viability, neovascularization, and hypoxia. Visual inspection of the xenograft shows drying and sloughing of the epidermis starting at week four. By week 12, the xenograft appears healed but has lost 63.05 ± 0.24% of the initial graft size. There is histologic evidence of epidermolysis as early as 2 weeks, which progresses until week 4, when new epidermis appears from the wound edges. Epidermal regeneration is complete by week 12, although the epidermis appears hypertrophied. An initial increase of infiltrating immune mouse cells into the xenograft normalizes to baseline 6 months after grafting. Neovascularization, as evidenced by positive staining for the proteins human CD31 and alpha smooth muscle actin, is present as early as 2 weeks after grafting at the interface between the xenograft and the mouse tissue. CD31 and alpha smooth muscle actin staining increased throughout the xenograft over the 12 weeks, leading to greater viability of the tissue. Likewise, there is increased Hypoxia Inducible Factor 1‐alpha expression at the interface of viable and nonviable tissue, which suggest a hypoxia‐driven process causing early graft loss. These findings illustrate human skin wound healing in an ischemic environment, providing a timeline for use of full thickness human skin after grafting in a murine model to study mechanisms underlying human skin wound healing.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
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        Journal Article
      ougenre: Article
    language: English
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