Abstract: Efforts to promote recovery of function after human spinal cord injury (SCI) will likely require interventions targeting the corticospinal tract (CST) motor system: the most important pathway for voluntary motor control in humans. This system has historically been the most refractory to regenerative efforts after SCI. The “non-regeneration” of the CST changed when robust regeneration of the CST into spared tissue was demonstrated by the inactivation of phosphatase and tensin homolog and delivery of inosine. However, a permissive growth matrix was required to achieve CST regeneration into a lesion site (Lu et al., 2012; Kadoya et al., 2016). This was provided by neural progenitor cell (NPC) grafts driven to spinal cord fates (Kadoya et al., 2016). Grafted NPCs differentiate to form new circuitry with the host spinal cord including neurons below the lesion site. However, these new circuits may not form appropriate connections with host neurons in the injured adult spinal cord due to a lack of spatial and temporal regulated axonal guidance cues present during development (Kaplan et al., 2014). Thus, the formation of these new connective circuits must be trained to form functional relays to reconnect the spinal cord and brain through appropriate targets.