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

Abstract

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.

Direct Thrombin Inhibition Reduces Lung Collagen Accumulation and Connective Tissue Growth Factor Mrna Levels in Bleomycin-Induced Pulmonary Fibrosis

“…Intra-alveolar accumulation of fibrin has been extensively documented in bleomycin-induced pulmonary fibrosis and in human studies of fibrotic lung disease, [2][3][4]53 and fibrin is thought to influence the fibrotic response by acting as a provisional matrix on which fibroblasts can proliferate and produce collagen in combination with fibronectin. 54 There is also evidence that fibrin can act as a reservoir of fibrogenic growth factors and cytokines that are released during fibrinolysis. 55 Fibrin has further been shown to protect active thrombin from inhibition from its physiological inhibitors so that it can remain available to exert its biological effects when bound to the provisional matrix.…”

Combined laparoendoscopic colon resection and anastomosis using the ``no touch technique'' and fibrin glue

“…Several studies have shown that human fibrin glue favors anastomotic collagen synthesis by promoting the hemostatic process and reducing collagenase activity through a specific inhibitor, the aprotinin [16]. Moreover, fibrin glue induces local migration of macrophages that produce factors promoting angiogenesis and fibroblast proliferation [14], and it also confines the bacterial flora within the colonic lumen, thereby limiting local sepsis [1,15].…”

Problems of fibrin adhesion of the nerves

“…Thrombin: Thrombin can have an inhibitory influence as well as a promoting influence on cell prolifferation depending on the point of time of its addition to fibroblast cultures [6,14,19,79,80]. The fibrosing effect demonstrated in our investigation …”

“…Theoretically, fibrosis could firstly be the result of direct influences of the adhesive's components, secondly an indirect effect of the clot in its entirety is conceivable. Hence, the objective of this study was to examine the effect of aprotinin [details: 3,5,26,29,31,34,36,39,48,53,59,104,105], thrombin [6,12,14,19,23,38,45,62,79,80,108,110], Factor XIII [2,4,7,13,14,15,24,32,46,52,60,61,70,74,77,84,92], fibronectin [14,27,30,33,44,47,69,74,75,…”