Benutzerspezifische Werkzeuge

B7: Niche targeting to increase graft size for allogeneic hematopoietic stem cell transplantation

Project leaders: Prof. Dr. G. Ehninger, Prof. Dr. Christian Thiede

The interaction of chemokines in the bone marrow niche and their receptors expressed on hematopoietic stem cells (HSC) is of major relevance for the mobilization and homing of HSC. During the last funding period, negatively regulating miRNAs of the CXCL12 (Stroma-derived factor 1, SDF-1) gene were identified. The physiological relevance of the expression of those miRNAs showed a critical function of miR-23 in the TGF-β pathway in MSC. Additionally a deregulation of β1-integrin targeting miRNAs with potential relevance for the interaction of HSC with the micro-environment was detected. With novel compounds interfering with the SDF-CXCR4 axis becoming available, this project will now focus on an unmet clinical need in the area of HSC stem cell transplantation. Many HSC harvests do not contain a sufficient amount of CD34 HSCs, which is a perquisite for a favourable outcome of the recipient. Overseeing more than 8,000 bone marrow and mobilized peripheral blood harvests and having a very active collection program will allow us (i) to identify novel clinical and molecular risk factors predicting poor mobilization of HSCs. (ii) In those donors with a poor bone marrow harvest or low CD34 dose apheresis, Plerixafor will be used within the context of a phase II trial. In addition, (iii) genome-wide association studies will be performed to identify novel factors predicting poor HSC mobilization.

 

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Funding program:

DFG