Genetic manipulation of neural stem cells for transplantation into the injured spinal cord.

The injured adult spinal cord is not conducive for neuronal regeneration and neurogenesis. Engrafted neural precursor cells (NPCs) differentiate largely into astroglia, with only a very small percentage becoming neurons (which might replace injured neurons) or oligodendroglia (which might improve injury induced demyelination of spared neurons). Several recent attempts have been made to enhanced neurogenesis or oligodendroglia differentiation of transplanted NPCs by genetic manipulation. These include exogenous expression of noggin, with the idea of antagonizing the astroglia differentiation promoting Bone Morphogenetic Proteins (BMPs). Direct attempts to enhance neurogenesis have also been made in transgenic over-expression of neurogenic basic helix-loop-helix transcription factors. These experiments resulted in some interesting observations, which we discuss here in the light of recent advances in development of cell-based engraftment therapy for spinal cord injuries.