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A nude mouse model of hypertrophic scar shows morphologic and histologic characteristics of human hypertrophic scar

Authors

  • Moein Momtazi MD, MSc,

    1. Division of Plastic and Reconstructive Surgery, University of Alberta, Edmonton, Alberta, Canada
    2. Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
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  • Peter Kwan MD,

    1. Division of Plastic and Reconstructive Surgery, University of Alberta, Edmonton, Alberta, Canada
    2. Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
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  • Jie Ding MD, PhD,

    1. Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
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  • Colin C. Anderson PhD,

    1. Alberta Diabetes Institute, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
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  • Dariush Honardoust PhD,

    1. Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
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  • Serge Goekjian BSc,

    1. Divisions of Plastic and Reconstructive Surgery and Critical Care, University of Alberta, Edmonton, Alberta, Canada
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  • Edward E. Tredget MD, MSc

    Corresponding author
    1. Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
    2. Divisions of Plastic and Reconstructive Surgery and Critical Care, University of Alberta, Edmonton, Alberta, Canada
    • Reprint requests:

      Dr. E. E. Tredget, 2D2.28 Walter Mackenzie Center, University of Alberta, 8440-112 Street, Edmonton, AB, Canada T6G 2B7.

      Tel: +1 780 407 6979;

      Fax: +1 780 407 7394;

      Email: etredget@ualberta.ca

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  • Presented at the Plastic Surgery Research Council 56th Annual Meeting, Louisville, KY, April 30, 2011.

Abstract

Hypertrophic scar (HSc) is a fibroproliferative disorder that occurs following deep dermal injury. Lack of a relevant animal model is one barrier toward better understanding its pathophysiology. Our objective is to demonstrate that grafting split-thickness human skin onto nude mice results in survival of engrafted human skin and murine scars that are morphologically, histologically, and immunohistochemically consistent with human HSc. Twenty nude mice were xenografted with split-thickness human skin. Animals were euthanized at 30, 60, 120, and 180 days postoperatively. Eighteen controls were autografted with full-thickness nude mouse skin and euthanized at 30 and 60 days postoperatively. Scar biopsies were harvested at each time point. Blinded scar assessment was performed using a modified Manchester Scar Scale. Histologic analysis included hematoxylin and eosin, Masson's trichrome, toluidine blue, and picrosirius red staining. Immunohistochemistry included anti-human human leukocyte antigen-ABC, α-smooth muscle actin, decorin, and biglycan staining. Xenografted mice developed red, shiny, elevated scars similar to human HSc and supported by blinded scar assessment. Autograft controls appeared morphologically and histologically similar to normal skin. Xenografts survived up to 180 days and showed increased thickness, loss of hair follicles, adnexal structures and rete pegs, hypercellularity, whorled collagen fibers parallel to the surface, myofibroblasts, decreased decorin and increased biglycan expression, and increased mast cell density. Grafting split-thickness human skin onto nude mice results in persistent scars that show morphologic, histologic, and immunohistochemical consistency with human HSc. Therefore, this model provides a promising technique to study HSc formation and to test novel treatment options.

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