Current status and prospects of regenerative medicine for spinal cord injury using human induced pluripotent stem cells: a review

Abstract

Spinal cord injury (SCI) is damage to the spinal cord due to trauma or health conditions, resulting in lesions in the spinal cord. Currently, available treatment includes surgical intervention to decompress or stabilize a dislocated loose spine, steroid drugs to reduce inflammation, and subsequent rehabilitation. As there is a rising number of SCI globally, radical treatments to recover spinal cord functions have become highly anticipated. The development of new treatments is indeed progressing. Various therapeutic drug candidates are being developed in clinical trials, including neuroprotective/neurotrophic factors, antibodies for repulsive guidance molecules, and cell transplantation. Among them, with advances in stem cell biology, cell transplantation therapy is currently a promising therapeutic development for SCI. In particular, there have been various reports regarding the realization of regenerative medicine using human induced pluripotent stem cells (iPSCs). This review will introduce the advantages of cell-based therapy based on iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs) and some of their mechanisms of action for functional improvement, which have recently been elucidated. Potential challenges and methodologies to realize the clinical application of iPSC-NS/PCs not only for the subacute phase but also for the chronic phase of SCI will be presented. Finally, we also introduce recent research with a view to the clinical application of spinal cord regenerative therapy and discuss future prospects.

Keywords: Spinal cord injury (SCI); cell-based therapy; induced pluripotent stem cells (iPSCs); neural stem/progenitor cells (NS/PCs); regenerative medicine.

Figure 1

Issues and solutions for achieving regenerative cell medicines derived from iPSCs. Several issues must be solved in each step, from establishing iPSC to after cell transplantation. Firstly, selecting a safety-validated iPSC line is essential without the risk of tumor formation. Second, each purpose’s optimal differentiation induction method should be adopted without contaminating undifferentiated and unintended differentiated cells. Thirdly, pre-clinical safety evaluation such as tumorigenicity and general toxicity is required before administration to patients. Fourth, immune rejection right after administration might be a problem. To overcome this hurdle, universal (HLA-modified) cell line or autologous transplantation would be helpful solutions. Finally, suicide gene transduction would be an alternative option to ablate transplanted cells to combat tumorigenesis following transplantation. iPSC, induced pluripotent stem cell; NS, neural stem; PC, progenitor cell; HLA, human leukocyte antigen.