Comparison of Regenerative Effects of Transplanting Three-Dimensional Longitudinal Scaffold Loaded-Human Mesenchymal Stem Cells and Human Neural Stem Cells on Spinal Cord Completely Transected Rats

Stem cell-based therapy has been considered as a potential treatment to restore spinal cord injury (SCI) through reconstructing neural networks and providing a favorable microenvironment for neuronal survival, differentiation, and axonal outgrowth. Biomaterial scaffolds can promote cell attachment and survival, neuronal differentiation, and axonal outgrowth; therefore, they were used to combine with stem cells for implantation in SCI treatment. In addition, a longitudinal scaffold can guide regenerated axons with orientated growth and axial extension. Both human umbilical cord-derived mesenchymal stem cells (hMSCs) and human fetal spinal cord-derived neural stem cells (hNSCs) have been applied in clinical trials worldwide. To our knowledge, a parallel comparison of the therapeutic effects of hMSC and hNSC implantations has not been conducted. Hence, in this study, we grafted hMSCs or hNSCs seeded on longitudinal collagen sponge scaffolds into rats with completely transected SCI to examine differences in SCI repair. Both hMSCs and hNSCs had equivalent effects on reducing glial scar formation around the lesion gap. More neuronal class III beta-tubulin-positive neurons and neurofilament-positive nerve fibers were found in the lesion cavity after hNSC implantation. In addition, hNSCs had better capabilities to improve motor function, attenuate inflammation, and promote cell survival than hMSCs. These encouraging results provide a clinical basis for future stem cell-based SCI therapies.