Abstract
Studies of multipotent neural stem cell (NSC) transplantations demonstrate their potential as a regenerative therapy to improve functional recovery following neurotrauma. However a major obstacle hindering greater tissue regeneration is the inefficient rate of engraftment and migration of transplant cells to the site of injury. Towards this challenge of improving NSC migration, other studies have discovered chemotactic or motogenic properties of certain trophic cytokines that are important for maintaining NSC multipotency. However fewer studies have investigated the use of physical migration cues, specifically direct current electric fields (EF) and even fewer look at the migratory responses of a combined chemical-electrical migration stimulation condition. In this study we compared the migration responses of human embryonic stem cell (ESC) line, H9, derived NSCs to chemical and electrical migration stimulation combinations in vitro. Our results suggests that trophic cytokines such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and adenosine triphosphosphate (ATP) traditionally known to induce a chemotactic response, did not have a positive chemokinetic effect on our H9-NSC migration. Conversely, exposure to direct current electric field stimulation enhances migration by increasing motility, migration directionality and distance travelled in a linear, less tortuous path. We also observed preliminary data that suggests contrary to intuitive expectations, electrical and EGF combined stimulation did not additively increase cell motility significantly or for any extended period of time. Interestingly, the co-stimulation appears to increase directedness of electrotactic migration. This suggests that other motogenic cytokines and electrical co-stimulation may positively enhance hNSC motility and directionality in vitro. It also suggests the combination could have similar effect on NSC migration if applied in vivo and warrants further study towards optimizing stimulation conditions. However because EF stimulation is the major contributing factor behind the increase in motility and linearity of migration path, the addition of a chemical component to optimize electrotaxis must be carefully considered due to complicated regulation behind receptor activation and downstream intracellular cascade signaling.