Neuronal reprogramming in treating spinal cord injury

Spinal cord injury (SCI) is a devastating neurological disorder that often impairs the daily function of patients for their entire life. While rodent SCI models have offered substantial understanding about the molecular and cellular mechanisms, there is still no effective therapy yielding significant functional recovery in SCI patients. In vivo neuronal reprogramming has recently emerged as a novel technology to regenerate new neurons from endogenous glial cells by overexpression of neurogenic transcription factors in the central nervous system (CNS). This approach completely eliminates the critical problem of immunorejection that the cell transplantation therapy is facing. The feasibility of in vivo neuronal reprogramming has been demonstrated successfully in models of different neurological disorders including spinal cord injury by numerous laboratories. Several reprogramming factors, mainly the pro-neural transcription factors, have been utilized to reprogram endogenous glial cells into functional neurons with distinct phenotypes.

• 1
  Sox2 has been shown to reprogram astrocytes and NG2 glia into proliferating neuroblasts, which can further differentiate into mature neurons with additional treatments.
• 2
  NeuroD1 can convert reactive astrocytes into functional neurons in the spinal cord dorsal horn with high efficiency.
• 3
  In vivo reprogramming may alleviate the glial scar formation by reducing the number of reactive glial cells and improving the inhibitory environment at the injury site for better endogenous regeneration.