DescriptionA third of human spinal cord injuries (SCIs) involve the lumbosacral spinal cord (LSC), but few studies are on LSC injury (LSCI) and no functional treatments are available to date. Unlike cervical or thoracic SCI that damages primarily the fiber tracts, LSCI disrupts both fiber tracts and neurons comprising the motor centers for walking, bladder, bowel and sexual functions. Thus, treatments for LSCI need not only axonal regeneration but also neuronal replacement. The ideal therapy is to transplant cells that have neuronal potential that can replace the damaged or lost neurons after LSCI. Initially, I cultured neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of neonatal Fischer 344 rats and other cell types as the sources for transplantation. However, those cells either remained as NSCs or produced astrocytes instead of neurons after transplantation. Neither lithium treatment nor silencing of the phosphatase and tensin homolog (PTEN) gene increased the percentage of neurons in culture. Silencing PTEN reduced neurons and produced more oligodendrocytes. Therefore, I transplanted human induced-pluripotent stem cell-derived neural stem cells (iPSC-NSCs) into immune-compromised Rowett nude (RNU) rats after LSCI. These human iPSC-NSCs survived, migrated and grew long processes 10 weeks after transplantation, showing the potential of human iPSC-NSCs as a future therapy for LSCI. However, the transplants did not improve functional recovery, and the reasons why will be discussed.