A novel model of humanised keloid scarring in mice

Abstract

Treatments for keloid scarring are a major challenge to scientists and physicians for their unknown aetiology. Although several models, including monolayer cell culture to tissue-engineered models, were developed, further research on keloid has more or less been hindered by the lack of appropriate animal models. Because these aberrant scars are specific to humans, we obtained human normal and keloid skin tissues and isolated dermal fibroblasts from them. Cell morphology, growth and immunohistochemical staining of myofibroblastmarker α-SMA were examined, and the cell medium of 2-hour culture and 24-hour culture was implanted on the back of nude mice. The cell medium of 2-hour culture and 24-hour culture was also analysed by a protein array for the detection of distinction in inflammatory factors. We showed that keloid fibroblasts had similar morphology and growth compared to normal skin fibroblasts, but the α-SMA expression was obviously up-regulated. After 6 weeks, mice of the 2-hour keloid-derived culture medium group exhibited keloid-like hypertrophic nodules macroscopically, while mice of 24-hour keloid-derived culture medium group were similar to normal skin. Histological findings confirmed that the reconstituted skin tissues had the typical features of human keloids. The protein array data revealed that RANTES were involved in humanised fibrotic occurrence in mice, also suggesting they were important modulators of this inflammatory event. This novel model might help to understand the key events that result in the formation of these abnormal scars and provide new therapeutic options.