Mesenchymal Stem Cells: Mechanisms of Spontaneous Transformation

Human bone marrow-derived mesencymal stem cells (MSCs) are considered highly important for tissue regeneration and repair. While these cells may have a considerable therapeutic potential, it is also possible that they may exert unwanted side effects by d eveloping cancer. We have during the last year made some striking observations: Within a group of normal MSC human donors, approximately 60% will spontaneously transform into cancer cells. The transformed mesenchymal stem cells develop over time into high ly tumorigenic cell populations, documented by the development of lethal metastases when injected into NOD/Scid mice. Our main objective is to characterize in detail the molecular mechanisms that lead to the spontaneous transformation of human MSCs, and by this determine to what extent MSC contribute to the formation of cancer. Sub-goals are to use gene silencing and over-expression strategies to interfere with putative genetic events that lead to malignant transformation.