Incorporating Combinatorial Approaches to Encourage Targeted Neural Stem/Progenitor Cell Integration Following Transplantation in Spinal Cord Injury

Spinal cord injury (SCI) severely diminishes quality of life and presents patients with a substantial financial burden. The lack of a curative treatment has guided efforts toward identifying potential regenerative treatments. Neural stem/progenitor cell (NSPC) transplantation represents a promising strategy for the regeneration of the injured spinal cord due to the ability of these cells to replace neural cells lost post-injury. However, the transplant-derived oligodendrocytes and neurons need to be able to associate and integrate within the appropriate endogenous circuits to guarantee optimal functional recovery. To date, the integration of these transplant-derived cells has lacked specificity and remains a challenge. As such, it appears that the transplanted cells will require additional guidance cues to instruct the cells where to integrate. In the present review, we propose a variety of combinatorial techniques that can be used in conjunction with NSPC transplantation to direct the cells toward particular circuits of interest. We begin by introducing distinct molecular signatures that assist in the formation of specific circuits during development, and highlight how favorable molecular cues can be incorporated within the cells and their environment to guide the grafted cells. We also introduce alternative methods including task-specific rehabilitation, galvanotaxis, and magnet-based tools, which can be applied to direct the integration of the grafted cells toward the stimulated circuits. Future research examining these combinatorial efforts may serve to improve outcomes following SCI.