Autor:innen:
Monika Wolny | Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum | Germany
Franziska Knüttgen | Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum | Germany
Dr. Katharina von Bargen | Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum | Germany
Tobias Flieder | Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum | Germany
Anne-Kathrin Vollmer | Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum | Germany
Prof. Dr. med. Cornelius Knabbe | Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum | Germany
PD Dr. Dr. Ingvild Birschmann | Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum | Germany
Background:
Maintaining integrity is essential for a biological organism. This is ensured by the complex mechanism of wound healing. If the natural course of wound healing is disturbed, the healing process may be delayed, or a chronic wound site may develop. In addition to conventional therapy, new strategies are being developed to treat, for instance, diabetic foot ulcers. A promising method is the application of platelets, the key players of hemostasis, in form of platelet-rich plasma. Furthermore, some coagulation factors have been associated with wound healing, e.g. FIXa could be associated in vitro with reduced cell adhesion and increased migration. In a mouse model it was shown that FXIII is involved in the healing of myocardial infarction. This indicates an important role played by coagulation factors in wound healing besides hemostasis.
Objective:
The aim of this study was to investigate the influence of a specific coagulation factor deficiency on dermal fibroblasts in vitro.
Methods:
Cell culture supernatant was supplemented with coagulation-factor-deficient plasma as a protein source. Two concentrations of plasma (20% and 60%) were used. Cell viability, proliferation and intracellular oxidative stress of dermal fibroblasts were evaluated in the absence of a specific coagulation factor. Furthermore, the gene expression of collagen I and IV, matrix metalloproteinase (MMP)2 and MMP9, tissue inhibitor of metalloproteinase (TIMP)1 and TIMP3, as well as the enzyme activity of MMP2 and MMP9, were investigated.
Results:
Cell proliferation, intracellular oxidative stress and enzyme activity of MMP2 and MMP9 did not show any significant changes dependent on specific coagulation factor deficiency. However, in first experiments gene expression of collagen I and IV, MMP2, MMP9 and TIMP1 was increased in cells incubated with plasma lacking FVII, FVIII, FIX or FX. Furthermore, cells showed a significantly increased viability when incubated with clotted supernatants (20% plasma lacking FVII, FVIII, FIX, FX, FXI, FXII or FXIII).
Conclusion:
Contrary to references in the literature, no significant effect of individual coagulation factors could be observed. However, the analyses indicate an influence of clot formation in the cell culture supernatant.