Tolerogenic Cellular Immunotherapy

We have established methods to generate and characterize tolerogenic antigen presenting cells (dendritic cells and macrophages) in human and rat and applied these in experimental renal transplantation models. In vitro experiments with human monocyte-derived DC concentrate on the immune regulatory mechanisms of corticosteroids and have a established a differential regulation of cytokines from the IL-12 family. Understanding of the fundamental mechanisms and local factors that influence skewing of myeloid precursor cells are key to the design and discovery of new strategies in preservation of organ transplants and dampening of ongoing immune and inflammatory responses.

For balanced use of immunosuppressive agents, it is of critical importance to have biomarkers which allow a close monitoring of the allo-specific immunity as well as of the ongoing inflammatory and injury response. We have an ongoing project (together with the department of Immunohematology) to evaluate and monitor the indirect pathway of allo recognition.

Clinical studies with mesenchymal stromal cells (MSC), as a strategy to safely taper immunosuppressive therapy, are ongoing within the department. These trials, making use both of autologous and allogenic MSC, are conducted in patients receiving a kidney of a living donor. We apply advanced strategies of frequent immune-monitoring to determine safety, efficacy and mechanism of action of this form of cell therapy.