Insights into the Molecular Mechanisms Regulating Cell Behavior in Response to Magnetic Materials and Magnetic Stimulation in Stem Cell (Neurogenic) Differentiation

Magnetic materials and magnetic stimulation have gained increasing attention in tissue engineering (TE), particularly for bone and nervous tissue reconstruction. Magnetism is utilized to modulate the cell response to environmental factors and lineage specifications, which involve complex mechanisms of action. Magnetic fields and nanoparticles (MNPs) may trigger focal adhesion changes, which are further translated into the reorganization of the cytoskeleton architecture and have an impact on nuclear morphology and positioning through the activation of mechanotransduction pathways. Mechanical stress induced by magnetic stimuli translates into an elongation of cytoskeleton fibers, the activation of linker in the nucleoskeleton and cytoskeleton (LINC) complex, and nuclear envelope deformation, and finally leads to the mechanical regulation of chromatin conformational changes. As such, the internalization of MNPs with further magnetic stimulation promotes the evolution of stem cells and neurogenic differentiation, triggering significant changes in global gene expression that are mediated by histone deacetylases (e.g., HDAC 5/11), and the upregulation of noncoding RNAs (e.g., miR-106b similar to 25). Additionally, exposure to a magnetic environment had a positive influence on neurodifferentiation through the modulation of calcium channels' activity and cyclic AMP response element-binding protein (CREB) phosphorylation. This review presents an updated and integrated perspective on the molecular mechanisms that govern the cellular response to magnetic cues, with a special focus on neurogenic differentiation and the possible utility of nervous TE, as well as the limitations of using magnetism for these applications.

Automated summary

Magnetic materials and stimulation have been widely studied in tissue engineering, especially in the reconstruction of bone and nervous tissue. Magnetic fields and nanoparticles can modulate cell responses and influence cellular structures and gene expression through complex mechanisms. The use of magnetic stimuli can promote stem cell evolution and neurogenic differentiation, as well as regulate calcium channels and CREB phosphorylation in neurodifferentiation. This review provides an updated perspective on the molecular mechanisms behind the cell response to magnetic cues and their potential applications in nervous tissue engineering.