Role of wound healing myofibroblasts on re-epithelialization of human skin

In human skin, large burned surfaces heal using two concomitant phenomena: re-epithelialization and dermal neoformation. Numerous studies report the r ole of interactions between keratinocytes and fibroblasts, but the relation ship between wound healing myofibroblasts and keratinocytes is not clear, e ven though these two cell types coexist during healing. We investigated the influence of myofibroblasts on keratinocyte growth and differentiation usi ng an in vitro skin model. A histological study was performed to determine the speed and quality of epithelialization. When the dermis was populated w ith fibroblasts, a continuous epidermis was formed in 7-10 days. In contras t, with wound healing myofibroblasts or without cell in dermis, the complet e re epithelialization never occurred over the 10-day period studied. After 7 further days of epidermal differentiation, histology showed an epidermis more disorganized and expression of basement membrane constituents was red uced when wound healing myofibroblasts or no cells were added in the dermis instead of fibroblasts. These results suggest that wound healing myofibrob lasts are not efficient to stimulate keratinocyte growth and differentiatio n. Treatment of fibroblasts with TGF beta 1 induced an increase of epiderma l cell differentiation as seen when myofibroblasts were present. However, t his cytokine did not change re-epithelialization rate and induced an increa se of basement membrane matrix deposition in opposition to myofibroblasts. Thus, TGF beta 1 action is not sufficient to explain all the different kera tinocyte reactions towards fibroblasts and wound healing myofibroblasts. Ou r conclusion is that myofibroblasts seem to have a limited role in the re-e pithelialization process and might be more associated with the increased ex tracellular matrix secretion. (C) 2000 Elsevier Science Ltd and ISBI. All r ights reserved.