Reconstitution of Human Keloids in Mouse Skin.

Abstract

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. 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. 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. The mouse model with humanized keloid tissue presented here should be a useful tool for future keloid research.