Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord

Exp Neurol. 2014 Mar:253:138-45. doi: 10.1016/j.expneurol.2013.12.022. Epub 2014 Jan 8.

Abstract

To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.

Keywords: Motor function; Neural precursor cells; Neuroprotection; Spinal cord injury; Transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Fetus
  • Gene Expression Regulation / physiology
  • HSP27 Heat-Shock Proteins / metabolism
  • Hindlimb / physiopathology
  • Humans
  • Motor Activity / physiology
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / physiology*
  • Neural Stem Cells / transplantation*
  • Pain Threshold / physiology
  • Rats
  • Spinal Cord / cytology*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / surgery*
  • Time Factors

Substances

  • HSP27 Heat-Shock Proteins
  • Nerve Tissue Proteins