Harnessing cold atmospheric plasmas: A novel therapeutic approach for liver fibrosis and tissue remodeling

• Applicant: Dr. Kristian Wende
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569255279

Chronic liver damage caused by viruses, alcohol abuse, metabolic disorders, and others can lead to liver fibrosis, where functional tissue is replaced by an excess of irregularly structured extracellular matrix. Over time, this can completely halt liver function (liver cirrhosis). The excessive activation of connective tissue cells, associated with a mismanaged immune response, is a substantial part of the problem. Current treatment is limited to addressing the underlying disease. This project proposal focuses on normalizing the cell activity of tissue-resident myofibroblasts regarding protein production and secretion, division rate, and signal transduction by influencing intra- and extracellular redox signals. To this end, a mixture of various reactive oxygen and nitrogen species generated by an endoscopically applicable plasma source will be used. The resulting cold atmospheric pressure plasma can be modulated in its reactivity over a wide range (e.g., by varying the working gas and power). Previous work has shown that cold plasmas can influence cellular signaling processes, for example, in the treatment of chronic wounds and the (experimental) treatment of cancer or precancerous lesions. The project aims to test this hypothesis. Using in vitro 2D and 3D cell models, in vivo models (mice), and ex vivo human tissue, the activity of myofibroblasts and their interaction with immune cells will be investigated. To gain insight into the pathophysiological processes, protein expression in the cell models and in the tissue will be examined, with particular consideration given to the proteins of the extracellular matrix. Additionally, the presence of (oxidative) post-translational protein modifications will be mapped, as these represent important signals for immune cells, myofibroblasts, and liver stellate cells and are involved in the manifestation of fibrosis. By optimizing the plasma source and studying transport processes between active plasma, subsequent effluents, and the cell or tissue models, the goal is to investigate which reactive species have the greatest impact on myofibroblasts. Overall, the aim is to examine the influence of cold atmospheric pressure plasmas and the reactive species they generate on the pathomechanisms of liver fibrosis in order to explore new options for therapeutic interventions.

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partners: Lynda Aoudjehane, Ph.D.; Professor Dr. Thierry Dufour; Dr. Laura Fouassier