Receptor-targeted, magneto-mechanical stimulation of osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.
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.
Institute of Science and Technology in Medicine, Guy Hilton Research Center, Keele University, Thornburrow Drive, Hartshill, Stoke on Trent, ST4 7QB, UK. jdobson@ufl.edu.
Bin
B
Hu
Alicia J
AJ
El Haj
Jon
J
Dobson
D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry; D010012:Osteogenesis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared
D039302:Integrin alphaVbeta3; D058185:Magnetite Nanoparticles; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D020796:Receptor, Platelet-Derived Growth Factor alpha