An in vivo model of wound healing in genetically modified skin-humanized mice.

Abstract

Cutaneous wound-healing disorders are a major health problem that requires the development of innovative treatments. Whithin this context, the search for reliable human wound-healing models that allow us to address both mechanistic and therapeutic matters is warranted. In this study, we have developed a novel invivo wound-healing model in a genetically modified human context. Our model is based on the regeneration of human skin on the back of nude mice by transplantation of a cultured bioengineered skin equivalent previously designed in our laboratory. In this setting, human keratinocytes in the epidermal compartment were genetically modified with a retroviral vector encoding the enhanced green fluorescent protein (EGFP). After stable engraftment of the EGFP skin was achieved (9-12 wk after grafting), a small circular full thickness wound was performed on this mature human skin. A wide variety of parameters involved in wound healing were monitored, including tissue architecture, cell proliferation, epidermal differentiation, dermal remodelling, and basement membrane regeneration. Wounded gene-targeted skin-humanized mice re-capitulated native skin wound-healing features. In addition, when keratinocyte growth factor (KGF), a growth factor that has been shown to improve wound healing, was added to wounds during 3 d, the re-epithelialization was significantly accelerated. The present wound-healing model system provides a suitable in vivo tool to test gene transfer strategies for human skin repair. It also serves as a complementary platform for studies in genetically modified mice and as a model to evaluate pharmaceutical therapeutic approaches for impaired wound healing.

• Authors: María José Escámez, Marta García, Fernando Larcher, Alvaro Meana, Evangelina Muñoz, Jose Luis Jorcano, Marcela Del Río
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 123 Issue 6 Pg. 1182-91 (Dec 2004) ISSN: 0022-202X [Print] United States
• PMID: 15610532 (Publication Type: Journal Article)

Chemical References

• FGF7 protein, human
• Fgf7 protein, mouse
• Fibroblast Growth Factor 7
• Fibroblast Growth Factors

Topics

• Animals
• Cell Differentiation
• Cell Division
• Cells, Cultured
• Dermis (cytology, injuries, physiology)
• Disease Models, Animal
• Epidermal Cells
• Epidermis (injuries, physiology)
• Extracellular Matrix (physiology)
• Fibroblast Growth Factor 7
• Fibroblast Growth Factors (pharmacology)
• Genetic Therapy
• Humans
• Keratinocytes (cytology, physiology)
• Mice
• Mice, Nude
• Regeneration (physiology)
• Skin Transplantation
• Tissue Engineering
• Wound Healing (drug effects, physiology)
• Wounds and Injuries (drug therapy, physiopathology)