Entwicklung einer optogenetisch kontrollierbaren MSC-Zelllinie für die präzise Regulation immunmodulatorischer Faktoren

Mesenchymal stem cells (MSCs) are being investigated as potential cell therapeutics because of their immunomodulatory properties. In this context, therapy with MSCs appears to show promise in the treatment of diseases with autoimmune and inflammatory components. However, the role of MSCs in the context of inflammatory diseases has not been adequately characterized. The tasks of toll-like receptors (TLR) on and in MSCs are varied and include the control of the proliferation and migration of the MSCs, the repair of damaged tissue, the promotion of angiogenesis and the regulation of the immune system. In this project we plan to build new cell lines from mesenchymal stem cells in which the specific signaling pathways of TLR 3 and 4 can be switched on and off with the help of optogenetics through light induction. The introduction of reporter genes also enables real-time detection of the signal pathways. The light-activatable cell lines obtained in this way are cultivated under physiological conditions (hypoxia and 3D culture) and both for their multipotency (stem cell character) and for the potential for pro-inflammatory (MSC1; TLR4 activation) or anti-inflammatory (MSC2; TLR3 activation) phenotypes train, tested. These two biological phenotypes will be precisely characterized with the help of multiplex ELISA, gene expression and quantitative proteome analyzes and compared with the phenotype of non-stimulated cells or primary cells. The competencies acquired within the scope of this project will strengthen the collaboration between the University of Natural Resources and Life Sciences, the IMC FH Krems and the LifeTaq-Analytics company, lead to further collaborations with biotech companies and contribute to a long-term expansion of the respective fields of competence in the field of regenerative medicine.