Substrate Dependent Galvanotaxis of Directly Reprogrammed Human Neural Precursor Cells

Adult neural precursor cells show great promise for the repair of central nervous system (CNS) tissue following injury or disease. Following injury to the CNS, endogenous neural precursor cells (NPCs), found in the neurogenic subventricular zone of the adult forebrain, are activated to proliferate and migrate toward the lesion site. However, this activation is not sufficient for neurorepair. Previous work has demonstrated that murine NPCs are electrosensitive cells that undergo rapid and cathodally directed migration in an applied electric field (EF). Here, we examined the EF induced migration of a clinically relevant human NPC population. With a goal of enhancing cell-based regeneration of the CNS, we explored the role of extracellular matrix (ECM) in human NPC behavior. NPCs plated on matrigel, MaxGel, laminin, and fibronectin were found to migrate in a substrate dependent manner. Common to all substrates was an increase in migration velocity in the presence of an EF. Different, was the direction of migration on the different substrates. The EF application did not induce differentiation on any of the substrates examined, as cells continued to express the precursor markers nestin and SOX2. We determined that secreted factors from neighbouring cells and extracellular pH were not significant factors in EF induced migration, however, substrate stiffness was sufficient to alter the direction of drNPC migration. These findings provide insight into factors that modulate human NPC migration and shed light on considerations for designing cell based therapies for neurorepair.