P.144 Comparative analysis of spinal cord-derived and induced pluripotent-derived neural stem & progenitor cells for SCI therapy

Background: Induced pluripotent stem cells (iPSCs) have revolutionized spinal cord injury (SCI) treatment by generating neural stem/progenitor cells (NSPCs). However, understanding how iPSC-derived NSPCs compare to authentic spinal cord NSPCs remains unclear. This study thoroughly characterizes bona fide spinal cord NSPCs and their isogenic iPSC-derived counterparts, iPSC-SC and iPSC-Br. Methods: Human spinal cord and skin tissue were obtained with ethics approval to establish primary NSPC cultures. iPSCs were derived from these primary cells and differentiated into iPSC-SC and iPSC-Br NSPCs. Assessments encompassed differentiation, proliferation capabilities, immunostaining, and RNA sequencing for differential gene expression. Results: Functional and transcriptional differences were identified between bona fide NSPCs and iPSC-SC/iPSC-Br. Bona fide and iPSC-SC NSPCs exhibited spinal cord regionalization, while iPSC-Br displayed forebrain regionalization. iPSC-derived NSPCs shared features reminiscent of early developmental stages, including embryonic patterning genes and increased proliferation rates. Notably, differentiation profiles were most similar between bona fide and iPSC-Br, with substantial distinctions observed between bona fide and iPSC-SC. Conclusions: This study unveils unique regional, developmental, and functional characteristics distinguishing spinal cord NSPCs from iPSC-derived counterparts. Addressing these disparities holds promise for enhancing iPSC-derived NSPC therapies in spinal cord injuries, contributing to a deeper understanding of their potential applications in regenerative medicine.