P.145 Uncovering differences in oligodendrogenesis between human and rodent spinal cord stem cells

Abstract

Background: Spinal cord regeneration in pre-clinical rodent studies is feasible by promoting oligodendrocyte regrowth, which is necessary for axon myelination. It is uncertain whether human neural stem/progenitor cells (NSPCs) are capable of differentiation into oligodendrocytes, similar to rat. In this study, we compare the functional and transcriptional features of primary spinal cord NSPCs from adult humans and rats. Methods: Oligodendrogenesis between human & rat NSPCs from adult donors and rats was cultured using the Neurosphere assay. NSPCs were exposed to 1% FBS to trigger differentiation & PDGF-AA to promote oligodendrocyte formation. Immunocytochemistry & RNA sequencing compared transcriptomes and analyzing differentially expressed genes. Results: Human NSPCs showed a reduced potential for oligodendrocyte generation compared to rat NSPCs (0.013±0.01% and 0.029±0.01% O4+ after one and two weeks in humans; 4.9±0.4% and 6.3±0.6% O4+ after one and two weeks in rats). PDGF-AA treatment at 40 ng/µL for one week was able to effectively promote oligodendrocyte differentiation in rat NSPCs, but had a minimal effect on human NSPCs (8.5±1.4 fold increase in O4+). OLIG1/2, SOX10, and CNP were enriched in rat NSPCs. Conclusions: We compared oligodendrogenesis potential between human and rat NSPCs and found significantly lower capacity in human NSPCs, possibly hindering successful myelinating techniques.