Bone Morphogenetic Protein-4 Influences Neural Differentiation of Induced Mouse Mesenchymal Stem Cells

Document Type : Original Article


1 Department of Cell and Molecular Biology, Cell Sciences Research Center, Royan Institute for Animal Biotechnology, ACECR, Isfahan, Iran

2 Department of Biology, University of Isfahan, Isfahan, Iran

3 Department of Stem Cells and Developmental Biology, Cell Sciences Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran


Objective: Members of the transforming growth factor-β superfamily, including bone morphogenetic protein 4 (BMP4), have been implicated as regulators of neural differentiation. The aim of this study was to establish whether BMP4 could influence neuronal differentiation of mesenchymal stem cells (MSCs).
Materials and Methods: Therefore, neuronal differentiation of MSCs was induced by basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) and treatment. The expression of neuronal specific markers such as Nestin, MAP2, β-Tubulin III and NKX6.1 were detected by RT-PCR, flow cytometery and/or immunostaining.
Results: While the percentage of Nestin positive cells was increased significantly during treatment, the addition of BMP4 during the first 4 days of treatment with bFGF and EGF reduced Nestin expression as showed by flow cytometry. This observation was further confirmed by relative gene expression which showed the reduction in expression of neural
markers such as Nestin, MAP2 and NKX6.1 following treatment with BMP4.
Conclusion: The results of this study suggest that BMP4 downregulates the neural fate of induced mouse MSCs.