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

Abstract

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.

Advances in Material‐Assisted Electromagnetic Neural Stimulation

“…Although these materials have not yet seen widespread use in clinical treatments, numerous pre‐clinical experiments have yielded positive results. [ 302 ] Specifically, we delve into the potential and specific therapeutic enhancements of materials‐assisted strategies at the pre‐clinical stage, focusing on their applications in brain, spinal cord, and peripheral nervous tissues.…”

The roles of neural stem cells in myelin regeneration and repair therapy after spinal cord injury

“…Continued studies should focus on extending cell sources, optimizing transplantation strategies and matching pre-clinical animal models with human SCI. In addition to cellular transplantation alone, combinatorial strategies based on NSCs such as co-transplantation therapies, cell delivery methods, enrichment of microenvironment, pharmacotherapeutics, biomaterial scaffolds and neurorehabilitation may have the potential to enhance injury repair following SCI [ 161 – 163 ]. We are confident that in the near future, NSCs have the potential to make remarkable breakthroughs in both the study of pathological mechanisms and clinical treatments for SCI.…”

Advancing Spinal Cord Injury Treatment through Stem Cell Therapy: A Comprehensive Review of Cell Types, Challenges, and Emerging Technologies in Regenerative Medicine

“…NSPCs can be derived from various sources, including embryonic and adult neural tissue, as well as iPSCs and ESCs ( Figure 1 ) [ 119 ]. These cells have the inherent ability to generate neural cells, including neurons, astrocytes, and oligodendrocytes [ 120 , 121 ]. NSPC transplantation has shown promise in preclinical studies, promoting functional recovery, reducing lesion size, and enhancing remyelination in animal models of SCI [ 36 ].…”