Regulation of neural markers nestin and GFAP expression by cultivated bone marrow stromal cells

Bone marrow stromal cells can differentiate into many types of mesenchymal cells, i.e. osteocyte, chondrocyte and adipocyte, but can also differentiate into non-mesenchymal cells, i.e. neural cells under appropriate in vivo experimental conditions (Kopen et al., 1999; Brazelton et al., 2000; Mezey et al., 2000). This neural phenotypic plasticity allows us to consider the utilization of mesenchymal stem cells as cellular material in regenerative medicine. In this study, we demonstrate that cultured adult rat stromal cells can express nestin, an intermediate filament protein predominantly expressed by neural stem cells. Two factors contribute to the regulation of nestin expression by rat stromal cells: serum in the culture medium inhibits nestin expression and a threshold number of passages must be reached below which nestin expression does not occur. Only nestin-positive rat stromal cells are able to form spheres when they are placed in the culture conditions used for neural stem cells. Likewise, only nestin-positive stromal cells are able to differentiate into GFAP (glial fibrillary acidic protein)-positive cells when they are co-cultivated with neural stem cells. We thus demonstrated that adult rat stromal cells in culture express nestin in absence of serum after passaging the cells at least ten times, and we suggest that nestin expression by these cells might be a prerequisite for the acquisition of the capacity to progress towards the neural lineage.