1 KMEB, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU2 Endocrinology, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU3 Aarhus Universitetshospital4 KMEB, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU5 Endocrinology, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU
INTRODUCTION Recently, the possibility that tumors originate from cancer stem cells (CSCs) has been proposed. Stem cells and CSCs share certain features such as self-renewal and differentiation potential. The aim of this study was to evaluate whether bone marrow stromal cells (BMSC) after long-term culture are transformed into malignant cells. MATERIAL AND METHODS BMSC from 6 pigs were isolated and propagated continuously. Cell morphology was observed. Transformation properties were evaluated by means of serum dependence assay, Ki- 67 immunostaining, soft agar colony assay, karyotyping, telomerase activity detection assay and analysis of the expression of p53, Fas and c- Myc genes. Multipotency was investigated by biochemical and histological assays and analysis of gene expression. RESULTS BMSC showed a change in appearance, from the initial spindle shape to a more flatted morphology then to small contact shape. After additional passages, BMSC gradually acquired recovery of proliferating capacity and transformation properties such as anchorage-independent growth, chromosomal abnormality, and abnormal gene expression. The expression of P53 and Fas was decreased, while the expression of c-Myc gene was increased and TGF‚ signaling pathway was upregulated. However, telomerase activity maintained negative during culture. CONCLUSION Porcine BMSC can undergo spontaneous transformation, which provides a useful model to study the mechanisms associated with the tumorigenic potential of adult stem cells.
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European Federation of National Associations of Orthopaedics and Traumatology, 2008