Molecular and cellular mechanisms of wound healing
01 / 2007 - unknown
Knowledge of the mechanisms and the sequence of events involved in hypertrophic scar formation might give clues for intervention to drive the healing process into tissue regeneration instead of scar formation. Hypertrophic scars are characterised by excessive collagen deposition and contraction. Fibroblasts and especially myofibroblasts are involved in this process. Myofibroblasts can arise from dermal fibroblasts through the action of growth factors (e.g. TGF-ß) released during the inflammatory phase. In normal wound healing without hypertrphic scar formation the myofibroblasts disappear through apoptosis. In hypertrophic scars the myofibroblasts remain present which suggests that there are differences in myfibroblast populations. For instance (myo-) fibroblasts migrating into the wound environment from the surrounding tissues such as subcutaneous fat might act differently in healing than dermal derived (myo-) fibroblasts. To test this hypothesis cells derived from different tissues (dermis, scar and subcutaneous fat) were isolated and expression patterns of genes involved in scar formation were determined (e.g. collagen types I and III, proteases and their inhibitors and a fibrotic tissue crosslinking enzyme). Cells derived from scar and subcutaneous fat showed similar expression levels of the different scar inducing genes (high collagen deposition low collagen degrading potency and fibrotic tissue type crosslinking). These levels differed from the expression levels observed in dermal cells. To be able to interfere in the healing process the sequence of scar inducing processes was studied in an animal wound healing model. Distinct expression patterns for the various genes were observed. For instance a disbalance between proteolytic enzymes and their inhibitors was observed in the healing wound in comparison with normal skin. The studies give indications at which level and in what processes interventions could be used to correct the altered homeostasis seen in scar formation in comparison with normal skin.