title: Utility of a human-mouse xenograft model and in vivo near-infrared fluorescent imaging for studying wound healing.
abstract: To study the complex cellular interactions involved in wound healing, it is essential to have an animal model that adequately mimics the human wound microenvironment. Currently available murine models are limited because wound contraction introduces bias into wound surface area measurements. The purpose of this study was to demonstrate utility of a human-mouse xenograft model for studying human wound healing. Normal human skin was harvested from elective abdominoplasty surgery, xenografted onto athymic nude (nu/nu) mice, and allowed to engraft for 3 months. The graft was then wounded using a 2-mm punch biopsy. Wounds were harvested on sequential days to allow tissue-based markers of wound healing to be followed sequentially. On the day of wound harvest, mice were injected with XenoLight RediJect cyclooxygenase-2 (COX-2) probe and imaged according to package instructions. Immunohistochemistry confirms that this human-mouse xenograft model is effective for studying human wound healing in vivo. Additionally, in vivo fluorescent imaging for inducible COX-2 demonstrated upregulation from baseline to day 4 (P = 0·03) with return to baseline levels by day 10, paralleling the reepithelialisation of the wound. This human-mouse xenograft model, combined with in vivo fluorescent imaging provides a useful mechanism for studying molecular pathways of human wound healing.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Shanmugam
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Tassi
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Marcel O
authors.initials: MO
authors.lastname: Schmidt
authors.affiliation: Division of Rheumatology, Immunology and Allergy, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: McNish
authors.affiliation: Center for Wound Healing and Division of Plastic Surgery, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.affiliation: Center for Wound Healing and Division of Plastic Surgery, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Attinger
authors.affiliation: Department of Biostatistics and Bioinformatics, MedStar Health Research Institute, Hyattsville, MD, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biostatistics and Bioinformatics, MedStar Health Research Institute, Hyattsville, MD, USA.
authors.forename: Nawar
authors.initials: N
authors.lastname: Shara
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Anton
authors.initials: A
authors.lastname: Wellstein
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016038:Skin Transplantation; D019265:Spectroscopy, Near-Infrared; D014183:Transplantation, Heterologous; D014945:Wound Healing / Q000502:physiology*; D014950:Wounds, Penetrating / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D005456:Fluorescent Dyes; D051546:Cyclooxygenase 2
keywords: COX-2; Mouse model; Wound healing; Xenograft