Targeting inflammation to support regeneration
The aim of this focus area is to understand the cell-cell interaction during inflammation that inhibits or supports endogenous regeneration in order to develop more specific targeting approaches.
Inflammation is a key factor for tissue regeneration following infection, major surgery, ischemia/reperfusion or trauma. Suppression of inflammation results in diminished protection against infection, reduced regeneration and wound healing. On the other hand, hyper-inflammation also inhibits stem/progenitor driven regeneration. To shape this process into a more balanced and protective intra-tissue inflammatory response, we need to improve our monitoring technologies and better understand the mechanisms of inflammation. Interestingly, MSC’s support endogenous regeneration less than by the direct replacement of injured tissue cells but more by indirectly supporting re-vascularisation, protecting tissue from stress-induced apoptosis and appropriately modulating inflammatory reaction. The extremely low immunogenicity of MSC’s makes them ideal candidates for the development of ‘off-the-shelf’ products for tissue regeneration. In addition, inflammatory cascades can be targeted or damped using multivalent approaches (Haag’s, Lendlein’s labs).
Studies on the crosstalk between immune cell subsets (cells of innate and adaptive immunity such as macrophages, DC´s, memory/effector and regulatory T cells and the complement system) and their products (cytokines, antibodies) on the one hand and the tissue, on the other hand, will be extended using clinically relevant experimental models and patients’ materials (Volk’s, Reinke’s, Sawitzki’s, Thiel’s, Scheibenbogen’s, Radbruch’s, Duda’s, Tschöpe’s, Spuler’s labs). Using in vivo monitoring, the processes of inflammation will be visualised (Haag’s, Dirnagl’s, Radbruch’s labs). Of particular interest is the understanding of long-term cell memory, the targeting of inflammatory terminally differentiated effector cells and supporting immune-regulation (Radbruch’s, Sawitzki’s, Thiel’s, Scheibenbogen’s, Volk’s, labs). In addition, studies on the interaction between immune system and stem cells (induced pluripotent- , embryonic- , hematopoietic- and mesenchymal- stem cells) and their derivatives are addressed more intensively in terms of immunogenicity and immune modulation using previously developed in vitro and in vivo (mouse models) systems (Volk’s, Reinke’s, Dragun’s, Tschöpe’s, Stamm's, Leutz’s lab). In particular, we aim to understand the mode of action of a particular MSC subset (PLX-1) that was successfully used in clinical trials at the BCRT. Finally, the development of well-validated biomarkers is an important issue in the promotion of personalised targeting of abnormally regulated inflammation.