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Title: Cyclic tensile loading regulates human mesenchymal stem cell differentiation into neuron-like phenotype
Authors: Leong, Wen Shing
Wu, Shu Cheng
Pal, Mintu
Tay, Chor Yong
Yu, Haiyang
Li, Huaqiong
Tan, Lay Poh
Issue Date: 2012
Source: Leong, W. S., Wu, S. C., Pal, M., Tay, C. Y., Yu, H., Li, H., et al. (2012). Cyclic tensile loading regulates human mesenchymal stem cell differentiation into neuron-like phenotype. Journal of Tissue Engineering and Regenerative Medicine, 6(S3), s68-s79.
Series/Report no.: Journal of tissue engineering and regenerative medicine.
Abstract: Mechanical loading has been utilized as an effective tool to direct mesenchymal stem cells (MSCs) commitment into cell lineages of mesodermal origin. However, the use of this tool to induce transdifferentiation of MSCs into the neural lineage has never been attempted. In this study, we examined the potential of uniaxial cyclic tensile loading in promoting neuronal differentiation of human MSCs (hMSCs) on modified biodegradable poly(ε-caprolactone) (PCL). The stem cell morphology, tissue-specific gene and protein expression, microfilament structure and, subsequently, Rho GTPase activity were analysed after cyclically stretching the cells at a range of amplitudes (0.5%, 2% or 3.5%) and frequencies (0.5, 1 or 1.5 Hz) for 8 h. hMSCs responded to these stimuli and displayed distinctly different microfilament organization. However, only those stretched at 0.5% strain amplitude and 0.5 Hz frequency showed promoted outgrowth of filopodia with significant upregulation of neurogenic genes expression. Positive staining of the neurogenic protein markers Nestin and Tuj1 suggested that the hMSCs had been committed to early neuronal progenitors. In addition, Rac1 but not RhoA was activated at this particular loading parameter. Furthermore, inhibition of Rac1 activity with NSC23766 disrupted the effect of cyclic loading. The results suggest that cyclic tensile loading at low amplitude and frequency is capable of triggering neuron-like differentiation through the regulation of Rho GTPases activity, even in the absence of neurogenic induction medium.
ISSN: 1932-6254
DOI: 10.1002/term.1548
Fulltext Permission: none
Fulltext Availability: No Fulltext
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