Recovery from paralysis in adult rats using embryonic stem cells

Ann Neurol. 2006 Jul;60(1):32-44. doi: 10.1002/ana.20901.


Objective: We explored the potential of embryonic stem cell-derived motor neurons to functionally replace those cells destroyed in paralyzed adult rats.

Methods: We administered a phosphodiesterase type 4 inhibitor and dibutyryl cyclic adenosine monophosphate to overcome myelin-mediated repulsion and provided glial cell-derived neurotrophic factor within the sciatic nerve to attract transplanted embryonic stem cell-derived axons toward skeletal muscle targets.

Results: We found that these strategies significantly increased the success of transplanted axons extending out of the spinal cord into ventral roots. Furthermore, transplant-derived axons reached muscle, formed neuromuscular junctions, were physiologically active, and mediated partial recovery from paralysis.

Interpretation: We conclude that restoration of functional motor units by embryonic stem cells is possible and represents a potential therapeutic strategy for patients with paralysis. To our knowledge, this is the first report of the anatomical and functional replacement of a motor neuron circuit within the adult mammalian host.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Cell Count
  • Cell Survival
  • Cells, Cultured / transplantation
  • Electrophysiology
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Graft Survival
  • Motor Neurons / cytology
  • Motor Neurons / physiology
  • Muscle, Skeletal / innervation
  • Nerve Regeneration / physiology
  • Neuromuscular Junction / physiology
  • Paralysis / physiopathology
  • Paralysis / therapy*
  • Rats
  • Rats, Inbred Lew
  • Recovery of Function*
  • Sciatic Nerve / cytology
  • Sciatic Nerve / physiology*
  • Spinal Cord / cytology
  • Spinal Cord / physiology*
  • Stem Cell Transplantation / methods*


  • Glial Cell Line-Derived Neurotrophic Factor