Reconstitution of Human Keloids in Mouse Skin

BACKGROUND: Keloids are a dermal fibroproliferative scar of unknown etiology. There is no good animal model for the study of keloids, which hinders the development and assessment of treatments for keloids. METHODS: Human keratinocytes and dermal fibroblasts were isolated from 3 human skin tissues: normal skin, white scars, and keloids. A mixed-cell slurry containing keratinocytes and dermal fibroblasts was poured into a double chamber implanted on the back of NOD/Shi-scid/IL-2Rγnull mice. After 12 weeks, the recipient mice had developed reconstituted human skin tissues on their backs. These were harvested for histological studies. RESULTS: Macroscopically, the reconstituted skins derived from both normal skin and white scars were similar to normal skin and white scars in humans, respectively. Keloid-derived reconstituted skins exhibited keloid-like hypertrophic nodules. Histological findings and immunohistochemical staining confirmed that the reconstituted skin tissues were of human origin and the keloid-derived reconstituted skin had the typical features of human keloids such as a hypertrophic dermal nodule, collagen type composition, orientation of collagen fibers, and versican expression. CONCLUSION: The mouse model with humanized keloid tissue presented here should be a useful tool for future keloid research.