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Receptor-Targeted, Magneto-Mechanical Stimulation of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells
Institute of Science and Technology in Medicine, Guy Hilton Research Center, Keele University, Thornburrow Drive, Hartshill, Stoke on Trent, ST4 7QB, UK
J. Crayton Puritt Family Department of Biomedical Engineering, Department of Materials Science and Engineering, Institute of Cell Engineering and Regenerative Medicine (ICERM), University of Florida, Gainesville, FL 32611, USA
* Author to whom correspondence should be addressed.
Received: 6 August 2013; in revised form: 2 September 2013 / Accepted: 5 September 2013 / Published: 23 September 2013
Abstract: Mechanical cues are employed to promote stem cell differentiation and functional tissue formation in tissue engineering and regenerative medicine. We have developed a Magnetic Force Bioreactor (MFB) that delivers highly targeted local forces to cells at a pico-newton level, utilizing magnetic micro- and nano-particles to target cell surface receptors. In this study, we investigated the effects of magnetically targeting and actuating specific two mechanical-sensitive cell membrane receptors—platelet-derived growth factor receptor α (PDGFRα) and integrin ανβ3. It was found that a higher mineral-to-matrix ratio was obtained after three weeks of magneto-mechanical stimulation coupled with osteogenic medium culture by initially targeting PDGFRα compared with targeting integrin ανβ3 and non-treated controls. Moreover, different initiation sites caused a differentiated response profile when using a 2-day-lagged magneto-mechanical stimulation over culture periods of 7 and 12 days). However, both resulted in statistically higher osteogenic marker genes expression compared with immediate magneto-mechanical stimulation. These results provide insights into important parameters for designing appropriate protocols for ex vivo induced bone formation via magneto-mechanical actuation.
Keywords: magnetic force bioreactor; tissue engineering; mechanotransduction; human mesenchymal stem cells; osteogenic differentiation
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Hu, B.; Haj, A.J.E.; Dobson, J. Receptor-Targeted, Magneto-Mechanical Stimulation of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells. Int. J. Mol. Sci. 2013, 14, 19276-19293.
Hu B, Haj AJE, Dobson J. Receptor-Targeted, Magneto-Mechanical Stimulation of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells. International Journal of Molecular Sciences. 2013; 14(9):19276-19293.
Hu, Bin; Haj, Alicia J.E.; Dobson, Jon. 2013. "Receptor-Targeted, Magneto-Mechanical Stimulation of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells." Int. J. Mol. Sci. 14, no. 9: 19276-19293.