Associated Principal Investigator, Director of Department for Dermatology and Venerology, University Hospital of Cologne
Prof. Dr. Thomas Krieg
Degenerative skin changes and poor wound healing occur more frequently in older people. The causes of chronic wounds and fragile skin are not yet fully understood. They are often associated with arterial or venous disease, diabetes mellitus and/or inflammatory skin disorders. Treating chronic wounds and their complications is a major medical and socioeconomic problem, and care for this patient group needs improvement.
Prof. Dr. Thomas Krieg’s research group explores the risk factors and mechanisms underlying chronic wounds aiming at the development of innovative therapies.
Our research: One key aspect is identifying factors of an increased risk to be affected from poor wound healing and chronic wounds, such as chronic venous insufficiency (CVI). This disease results in inflammatory and fibrotic changes to the skin, which often trigger tissue loss and chronic wounds on the calves and feet. Prof. Krieg and his team of scientists are working to understand the mechanisms of cellular communication and use these findings to help identify the processes that promote degenerative changes in the skin and inhibit the normal healing process.
Our successes: Wound healing mechanisms are regulated by the immune system. Using new mouse models, Prof. Krieg and his working group have successfully proven that specific macrophage populations play a key role in the different wound healing processes and that regulating these influences the quality of the wound healing response.
Additionally the team has shown that mast cells, whose part in triggering fibroses has long been a point of discussion, play more of a subordinate role. The researchers achieved another breakthrough with the identification of new interactions among extracellular matrix molecules in fibrotic skin diseases and with the characterization of the functional consequences for scar formation.
Our goals: The team’s basic research has already identified a number of mechanisms essential to the normal wound healing process. Disruptions of these cellular and molecular reciprocal interactions are implicated in chronic wounds and fibrotic disorders. The aim is to use these findings to test therapeutic approaches in the clinic with the ultimate objective of developing a treatment for chronic wounds while limiting scar formation as much as possible.
Our methods/techniques: Prof. Krieg’s group uses a variety of experimental approaches. Cell biology methods and molecular techniques in particular are used in basic research. Based on the results from experiments with cell cultures, transgene mice are investigated preclinically as model organisms before new, very promising therapeutic approaches can be tested in clinical studies.
Figure 1: Macrophage depletion during the early stage of repair attenuates epithelialization, granulation tissue formation and scar formation.
H&E stainings of wounds in control (LysMCre) and macrophage depleted mice (LysMCre/iDTR) at indicated time points after injury. Whereas in control mice, the day-5 wound is filled with a vascularized granulation tissue in LysMCre/iDTR mice only scarce granulation tissue has formed (black hatched line outlines granulation tissue, white dotted line outlines hyperproliferative epithelial tongue); day-14 wounds in control and LysMCre/iDTR mice are closed, scar tissue is minimal in LysMCre/iDTR mice (hatched line outlines scar tissue).