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Open Access Research article

Regulation of nestin expression by thrombin and cell density in cultures of bone mesenchymal stem cells and radial glial cells

Franz Wautier1, Sabine Wislet-Gendebien1, Grazyna Chanas1, Bernard Rogister123 and Pierre Leprince1*

Author Affiliations

1 Center for Cellular and Molecular Neurobiology, University of Liège, CHU B36, Avenue de l'Hôpital, 1, B-4000 Liège, Belgium

2 Department of Neurology, University of Liège, CHU B35, B-4000 Liège, Belgium

3 Department of Biochemistry and Cell Physiology, University of Liège, CHU B35, B-4000 Liège, Belgium

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BMC Neuroscience 2007, 8:104  doi:10.1186/1471-2202-8-104

Published: 30 November 2007

Abstract

Background

Bone marrow stromal cells and radial glia are two stem cell types with neural phenotypic plasticity. Bone marrow mesenchymal stem cells can differentiate into osteocytes, chondrocytes and adipocytes, but can also differentiate into non-mesenchymal cell, i.e. neural cells in appropriate in vivo and in vitro experimental conditions. Likewise, radial glial cells are the progenitors of many neurons in the developing cortex, but can also generate astrocytes. Both cell types express nestin, an intermediate filament protein which is the hallmark of neural precursors.

Results

In this study, we demonstrate that thrombin, a multifunctional serine protease, stimulates the growth of radial glial cells (RG) and mesenchymal stem cells (MSCs) in a dose-dependent manner. In RG, the mitogenic effect of thrombin is correlated with increased expression of nestin but in MSCs, this mitogenic effect is associated with nestin down-regulation. Both cell types express the PAR-1 type receptor for Thrombin and the effect of Thrombin on both cell types can be mimicked by its analogue TRAP-6 activating specifically this receptor subtype or by serum which contains various amount of thrombin. Moreover, we also demonstrate that serum deprivation-induced expression of nestin in MSCs is inhibited by high cell density (> 50,000 cells/cm2).

Conclusion

This work shows that thrombin stimulates the growth of both RG and MSCs and that nestin expression by MSCs and RG is regulated in opposite manner by thrombin in vitro. Thrombin effect is thus associated in both cell types with a proliferating, undifferentiated state but in RG this involves the induction of nestin expression, a marker of immaturity for neural progenitors. In MSCs however, nestin expression, as it corresponds to a progression from the mesenchymal "undifferentiated", proliferating phenotype toward acquisition of a neural fate, is inhibited by the mitogenic signal.