Fucoidan Modulates the Effect of Transforming Growth Factor (TGF)-.BETA.1 on Fibroblast Proliferation and Wound Repopulation in in Vitro Models of Dermal Wound Repair

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Abstract
Aberrant wound healing, either causing scarring or chronic wounds, is a significant cause of morbidity. There is therefore, considerable interest in agents which can modulate certain aspects of the wound healing process. Fucoidans, sulphated polyfucose polysaccharides which may be extracted from Fucus spp., have been shown to modulate the effects of a variety of growth factors through mechanisms thought to be similar to the action of heparin. We investigated the interaction between two commercial preparations of fucoidan and transforming growth factor (TGF)-beta(1). These preparations of fucoidan, as well as heparin, inhibited fibroblast proliferation at concentrations from 0.01 to 100 mg/ml. The anti-proliferative effects of 1 ng/ml TGF-beta(1) on dermal fibroblasts were abrogated by fucoidan preparation F7 when used at concentrations over 1 mg/ml. In a three dimensional in vitro model of wound repair, the fibroblast populated collagen lattice or "dermal equivalent", TGF-beta(1) reduced the rate of fibroblast repopulation of a wound defect created by punch biopsy. Addition of fucoidan to the model in the presence of TGF-beta(1) increased the rate of fibroblast repopulation of the wound and at 10 mg/ml of fucoidan the number of cells which had migrated into the wounded defect was similar to that of control cultures. These data suggest that fucoidan has properties which may be beneficial in the treatment of wound healing.