Comparison of Spinal Cord-Derived Endogenous Stem Cells Versus Induced Pluripotent Stem Cells for SCI Therapy

Introduction: Induced pluripotent stem cells (iPSCs) have revolutionized spinal cord injury (SCI) treatment by enabling the creation of neural stem/progenitor cells (NSPCs). However, a comprehensive understanding of how iPSC-derived NSPCs compare to authentic spinal cord NSPCs in molecular and functional terms remains elusive. Our study aims to provide a comprehensive characterization of bona fide spinal cord NSPCs and their isogenic iPSC-derived counterparts, specializing in the spinal cord (iPSC-SC) and the brain (iPSC-Br).

Methods: We obtained human spinal cord and skin tissue with ethics approval, subsequently establishing primary neural stem/progenitor cell (NSPC) cultures. From these primary cells, we derived induced pluripotent stem cells (iPSCs) and differentiated them into brain-regionalized (iPSC-Br) and spinal cord-regionalized (iPSC-SC) NSPCs. We assessed these cells for various characteristics, including their differentiation and proliferation capabilities, using immunostaining and RNA sequencing to identify differential gene expression and functional changes.

Results: Significant differences were identified in the functional and transcriptional properties of bona fide NSPCs compared to iPSC-SC and iPSC-Br. Bona fide and iPSC-SC NSPCs exhibited spinal cord regionalization, whereas iPSC-Br displayed a dorsal forebrain regionalization. Notably, iPSC-derived NSPCs shared functional and transcriptional features reminiscent of early developmental stages, including embryonic patterning genes and increased proliferation rates. Moreover, differentiation profiles were most similar between bona fide and iPSC-Br, while substantial distinctions were observed between bona fide and iPSC-SC.

Conclusion : Our study unveils unique regional, developmental, and functional characteristics differentiating bona fide spinal cord NSPCs from iPSC-derived NSPCs. Addressing these disparities holds promise for enhancing the clinical effectiveness of iPSC-derived NSPC therapies for spinal cord injuries. This investigation sheds light on the distinct attributes of these two cell types, contributing to a deeper understanding of their potential applications in the realm of spinal cord injury treatment and regenerative medicine.