Effect of p144@ (anti-TGF-B) in a "in vivo" human hypertnophic scars model in nude mice

Abstract

Background Hypertrophic scars are one of the most relevant complications in surgery due to their cosmetic and functional impairments. Among the cytokines responsible of this anomalous healing, Transforming Growth Factor-beta (TGF-ß) has been demonstrated to be one of the most representative. Previous studies in tissue fibrotic disorders have shown promising results by inhibiting the biological activity effect of TGF-ß. The objective of the current study is to determine the effect of the inhibition of TGF-ß1 signaling in human hypertrophic scars implanted in nude mice by topical application of a TGF-ß1 receptor type III inhibitor peptide (P144®). Material and methods 30 human hypertrophic scars were implanted in 60 mice. The animals were divided into two groups, group A (placebo) and group B (treatment). Group C (basal) was considered as the preimplanted scar tissue samples. When all the xenografts were shed, topical application of a lipogel containing placebo (group A) or P144 (group B) was daily administered during 15 consecutive days. After the completion of the treatment, the animals were sacrificed and the total area, scar thickness and collagen fibers area of the scars were compared across all groups. Immunocytochemistry was performed to quantify the collagen type I and III production and fibrillin-1 to determine elastic fibers present in the dermis. Results 83,3% of the xenografts shed successfully. The mean time for shedding was 35±5.4 days. Statistical differences were found in the total area, thickness and collagen fibers area in the comparison between the groups. Reduction in 10% of total area of the scars was achieved with the treatment in comparison with the placebo group. An increase in the expression of fibrillin-1 and decrease in collagen I were found when comparing treatment group with the basal group. Conclusions Topical application of the inhibitor of TGF-ß1 seemed to be promising in an �in vivo� model of human hypertrophic scars implanted in nude mice given that enhancing of scar maturation was found with a decrease in dermal collagen fibers and an increase in elastic fibers. Although increasing knowledge in the pathogenesis of hypertrophic scars has been achieved for many decades, it is clear that there is still a lack of an ideal animal model that would allow understanding this disease in a more holistic approach. Consequently, a more extensive knowledge of the pathogenesis would help to focus the new therapies on modulating the fibrotic disorders pathways.