Effect of IGF-beta 2 on proliferative scar fibroblast cell kinetics

Keloids, hypertrophic scars, and burn hypertrophic scars are all forms of p roliferative scarring characterized by overabundant matrix formation. Recen tly these dermal proliferative disorders have been linked clinically to the cytokine transforming growth factor beta (TGF-beta), and in vitro tests ha ve shown it to be responsible for the activation of fibroblasts and their p roduction and deposition of collagen. Using an established in vivo animal m odel of proliferative scarring, the effects of this cytokine, specifically the isoform TGF-beta 2, on these scars were examined. Proliferative scar sp ecimens were implanted into athymic, asplenic nude rats and isolated in san dwich island flaps based on the superficial inferior epigastric pedicle. Af ter establishment of the transferred flap, the scars were injected with var ying doses of TGF-beta 2 or vehicle for 5 consecutive days and then again o n days 10, 15, and 20. The specimens were measured weekly during the period of dosing, and a biopsy was acquired on days 30 and 60. Fibroblasts from t he explanted biopsies and the original scars were grown in cell culture, an d cell proliferation studies were performed and the results compared. There was a dose response to TGF-beta 2, with 200 ng showing the greatest effect . From the original scar specimens, keloid scars demonstrated the greatest cell proliferation kinetics-significantly faster than nonburn and burn hype rtrophic scars. After treatment with TGF-beta 2, both keloids and burn hype rtrophic scars showed an increase in their cell proliferation kinetics comp ared with vehicle alone. This was not demonstrated with the nonburn hypertr ophic scars. Elevated levels of TGF-beta 2 are a major contributing factor to the process of proliferative scars, but because nonburn hypertrophic sca rs do not result in an equally increased response to this cytokine, a truly causative role for this cytokine cannot be promulgated. Rather, it is the combination of the proliferative scar fibroblasts' abnormal response to TGF -beta 2 stimulation and elevated levels of this cytokine that controls more accurately the process of keloid and burn hypertrophic scar formation.