Treatment of steroid resistant grade II to IV acute GVHD by infusion of mesenchymal stromal cells expanded with platelet lysate - a phase I/II study

Additionally, we show that MIF is able to upregulate the expression of cytokines described as chemoattractants for MSC (IL8, IL6 and CCL2), reinforcing the role of this molecule as the first trigger for several downstream signalling pathways. Importantly we show that knock down (using lentiviral shRNAs) of either CXCR4 (in MSCs) or MIF (in cancer cells) decreases significantly MSC homing to tumors in an in vivo pulmonary metastasis model. Interestingly, MIF has been shown by others to be over-expressed in a large variety of human cancers and closely correlates with tumor aggressiveness and metastatic potential. Therefore, MSC homing to tumors triggered by MIF could be a general mechanism for a variety of cancers. This improved understanding of MSC tumor tropism will further enable development of novel cellular therapies for cancers by increasing the homing potential of these cells.