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STAMCELLER-Stamcelleforskning

Cancer and Mesenchymal Stem Cells

Awarded: NOK 3.5 mill.

Mesencymal stem cells (MSCs) isolated from the human bone marrow, have been suggested, based on their differentiation potential, to be used in tissue regeneration and repair strategies. While these cells may have a considerable therapeutic potential, it i s also possible that they may have unwanted side effects as for instance by developing cancer. We have during the last year made some striking observations: Within a group of normal MSC-human donors, approximately 50% will spontaneously transform into can cer cells. This occurs when the MSC cells are entering the senescence stage. By spectral karyotyping and array comparative genomic hybridization, of the transformation events we show that just before transformation the MSCs develop a pure tetraploid karyo type, without any chromosomal translocations. After a few passages, chromosomal translocations appear, leading to highly tumorigenic cell populations when implanted in NOD/Scid mice. Preliminary results suggest that aneuploidy appear before genetic insta bility. The mechanism behind the development of the tetraploid karyotype is not known but can be explained by cell fusion phenomena or by incomplete cell division. The group has developed advanced GFP expressing NOD/Scid animal models to study these event s. We are also in the process of performing detailed genetic analyses of the transformation event. Interestingly, Notch, BMI-1, SKP2 and telomerase activity is up-regulated in the transformed cells. To functionally study the mechanisms behind the transfo rmation events we will use knock-out and over expression strategies. Besides providing important knowledge related to cancer initiation and development, the project will provide vital information regarding the establishment of putative safety measures in cell thearpies using MSCs.

Funding scheme:

STAMCELLER-Stamcelleforskning