Thrombin and fibrin-induced growth of fibroblasts: role in wound repair and thrombus organization.

Skin fibroblast cultures were treated with various components of the blood clotting system (thrombin, fibrinogen and fibrin) during the logarithmic growth phase. Fibrin as well as thrombin showed dose-dependent growth promoting activities as revealed by cell counting and 3H-thymidine uptake. No effect was seen with fibrinogen. After entrapping in polymerizing fibrin enriched by complete culture medium the cells elongated, multiplied and formed net-like interconnecting cell strands throughout the clots. Nutritional deprivation appeared as a limiting factor for eventual growth cessation. The results demonstrate active growth of fibroblasts in fibrin clots such as present in healing wounds and thrombi. The production of thrombin by the coagulation cascade does not only result in the conversion of fibrinogen to fibrin but has also a long-lasting hormone-like effect on fibroblast proliferation which is of essential importance in wound healing, thrombus organization and progression of chronic atherosclerotic lesions.