Signalling pathway in the induction of neurite outgrowth in human mesenchymal stem cells

• Published in: Cellular signalling 2006-04, Vol.18 (4), p.519-530
• Main Authors: Chu, Mien-Sheng, Chang, Ching-Fang, Yang, Chuan-Ching, Bau, Yi-Chi, Ho, Larry Low-Tone, Hung, Shih-Chieh
• Format: Article
• Language: English
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; cAMP–PKA; Colforsin - pharmacology; Cyclic AMP Response Element-Binding Protein - metabolism; Cyclic AMP-Dependent Protein Kinases - drug effects; Cyclic AMP-Dependent Protein Kinases - metabolism; Female; Human mesenchymal stem cells; Humans; Immortalization; MAPK–ERK; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Middle Aged; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Neurite outgrowth; Neurites - drug effects; Neurites - metabolism; Neuroepithelial cells; Phosphorylation; Signal Transduction - drug effects; Signal Transduction - physiology; Time Factors
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2005.05.018

Recent in vivo transplantation studies have shown that mesenchymal stem cells (MSCs) were able to differentiate into mesoderm-derived cell types as well as cells with neuroectodermal characteristics, suggesting that transdifferentiation occurs in the mammalian system. We have reported an immortalized line of human MSCs (hMSCs), KP-hMSCs, which expresses CD29, CD44, CD90, and CD105, and complies with the characteristics shared by mere hMSCs. In a current experiment, we further demonstrated that expanded KP-hMSCs exhibited markers of neuroepithelial or neural precursor cells, such as Nestin, Musashi-1, Vimentin, NCAM, Pax-6, and Sox-9. KP-hMSCs simultaneously expressed proteins of the neuronal, astrocyte, and oligodendrocyte lineages during culture expansion; in addition, they initiated neurite outgrowth and eradicated protein expressions of astrocyte and oligodendrocyte lineages in response to the elevated signaling of the cAMP–PKA pathway after serum depletion in a defined neural induction medium. From the current results, KP-hMSCs may be used to elucidate molecular signaling on the neural differentiation of adult human non-neural tissues. We also presented evidence for the possibility that adult MSCs and fetal neuroepithelial or neural precursor cells both provide for the continual maintenance and repair of the postnatal neural tissues and may derive from the same origin or have one deriving from the other.