Pharmacological therapy of keloids in an athymic mouse model

In spite of the high incidence of dermal fibroproliferative disorders, there is no agreement about the treatment of choice. Due to the inability of animals to produce keloid tissue, a standardised model to study the effects of different treatment modalities in vivo is lacking. Therefore, a comparative study on the effect of three pharmacological agents was conducted with human keloid implants in an athymic mouse model. Cubic keloid tissue blocks from 10 human volunteers were implanted in 54 male, athymic, homozygotic mice. The animals were divided into 4 groups, including an untreated control group. Members of each section received either colchicine, nicardipine or triamcinolone applied transdermally into the keloid tissue or into the peritoneum. The tissue specimens of 5 mice each were explanted according to a predetermined time schedule on days 28, 42 and 56 post-implantation and examined using various histological techniques including standard dye and immune histochemistry. The freeze-dried and moist weights of the keloid tissue were determined and analysed. Statistically significant changes regarding declining weight parameters were seen in the colchicines-treated group. Moreover, the densities of fibroblasts and endothelial cells were significantly reduced through colchicines treatment when compared to the control group and the groups treated with the other agents. The triamcinolone group also showed partially significant changes of weight compared to the control group, whereas no statistically significant effect of nicardipine on any parameter was found. Any influence of the host organism could be excluded as there were no signs of rejection or lymphocytic infiltration. Our study represents a successful attempt to create a standardised model for a comparative investigation on keloid tissue in vivo. The effect of colchicine was demonstrated in the light of an inhibitory effect on fibroblastic proliferative activity. The studied model allows a direct comparison of implanted, vascularised keloid tissue and its reactivity to various agents without being biased by numerous unknown variables in humans.