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A Novel Nude Mouse Model of Hypertrophic Scarring Using Scratched Full-Thickness Human Skin Grafts

  • Author / Creator
    Alrobaiea, Saad Mohammad
  • Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder that develops following deep skin injury. This dermal fibrosis can cause deformities, functional disabilities, and aesthetic disfigurements. The pathophysiology of HTS is not understood due in part, to the lack of an ideal animal model. We hypothesize that human skin with dermal wounds of a depth known to reproducibly cause HTS once grafted onto athymic nude mice will develop a raised elevated scar similar to HTS seen in humans. Our aim is to develop a representative animal model of human HTS and to explore the cellular origin of the fibrosis either locally derived from the deep dermal human fibroblasts or from the bone marrow derived monocytes of the mouse. Thirty-six nude mice were grafted with full thickness human skin with deep dermal scratch wound before or 2 weeks after grafting. The scratch on the human skin grafts was made using a specially designed jig creates a wound > 0.6 mm in depth which has been demonstrated to be the depth of injury in human skin volunteers beyond which HTS consistently develops. Deep dermal wounds in the human skin grafts transplanted on to the dorsal surface of athymic mice were morphologically analyzed by digital photography. Mice were euthanized at one, two, and three months postoperatively before histological analysis of scar thickness, collagen synthesis and fiber orientation, mast cells, macrophages, human leukocyte antigen-ABC, and myofibroblasts was performed. Morphologic persistence of human fibroblasts in the raised elevated scar was documented up to one-year post engraftment using human anti-ABC antibodies. The mice developed red, raised, and firm scars in the scratched xenografts with more contraction, increased recruitment of macrophages and myofibroblasts as compared to the xenografts without deep dermal scratch wound. Scar thickness and collagen bundle orientation and morphology were resembled that seen in human HTS in the deep dermal wounds within the engrafted human skin on the dorsum of the mice. The fibrotic scars in the wounded human skin were morphologically and histologically similar to human HTS and human skin epithelial cells and fibroblasts persisted in the remodelling tissues for at least one year post-engraftment. Thus, deep dermal injury in human skin retains its profibrotic nature after transplantation, affording a novel model for the assessment of therapies for the treatment of human fibroproliferative disorders of the skin.

  • Subjects / Keywords
  • Graduation date
    2015-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3VX06B2V
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Department of Surgery
  • Supervisor / co-supervisor and their department(s)
    • Dr. Colin Anderson (Department of Surgery)
    • Dr. Jie Ding (Department of Surgery)
    • Dr.Edward E. Tredget (Department of Surgery)
  • Examining committee members and their departments
    • Dr. Tom Churchill (Department of Surgery)
    • Dr. Edward E. Tredget (Department of Surgery)
    • Dr. Colin Anderson (Department of Surgery)
    • Dr. Jie Ding (Department of Surgery)