1. Treatment of Steroid Resistant Grade II to IV Acute GVHD by Infusion of Mesenchymal Stroma Cells Expanded with Platelet Lysate - a Phase I/II Study
- Author
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L. E. van der Wagen, L. C. J. te Boome, Eefke Petersen, Caroline A. Lindemans, J.J. Boelens, Kasper Westinga, Marc Bierings, NM Wulffraat, C. Mansilla, Eric Spierings, Marloes Cuijpers, Ineke Slaper-Cortenbach, and J. Kuball
- Subjects
Cancer Research ,Transplantation ,integumentary system ,business.industry ,Immunology ,Mesenchymal stem cell ,Cell Biology ,Hematology ,CCL2 ,CXCR4 ,surgical procedures, operative ,Oncology ,Downregulation and upregulation ,hemic and lymphatic diseases ,Cancer cell ,Immunology and Allergy ,Medicine ,Platelet lysate ,Interleukin 8 ,business ,Genetics (clinical) ,Homing (hematopoietic) - Abstract
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.
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