Human hypertrophic scar-like nude mouse model: characterization of the molecular and cellular biology of the scar process.

Hypertrophic scar (HTS) following thermal injury and other forms of trauma is a dermal fibroproliferative disorder that leads to considerable morbidity. Because of the lack of an ideal animal model, research is difficult. We have established an HTS model that involves transplanting human split-thickness skin graft (STSG) or full-thickness skin graft (FTSG) onto the backs of nude mice. The animals developed raised, firm, and reddish scars 2 months following transplantation. Histology and micromeasurement indicate raised, thickened engrafted skin with STSG and FTSG. In contrast, thickening was not observed with full-thickness rat skin grafts used as controls. Masson's trichrome staining demonstrates increased accumulations of collagen fibrils in the dermis in both scars grafted with STSG and FTSG. Staining cells with toludine blue and an antibody for F4/80 showed an increase in the infiltration of mast cells and macrophages. Quantification of fibrocytes reveals increased fibrocytes. Moreover, STSG grafted skin had significantly more macrophages, mast cells, and fibrocytes than FTSG. Real-time polymerase chain reaction analysis showed significantly elevated mRNA levels for type I collagen, transforming growth factor-β, connective tissue growth factor and heat shock protein 47 in both types of engrafted skin. These data demonstrate that human skin grafted onto nude mice develops red raised and thickened scars having intrinsic properties that closely resemble HTS formation as seen in humans. Interestingly, STSG developed more scar than FTSG. Furthermore, inflammatory cells and bone marrow-derived fibrocytes may play a critical role in HTS development in this animal model.