Recovery from paralysis in adult rats using embryonic stem cells
DM Deshpande, YS Kim, T Martinez… - Annals of …, 2006 - Wiley Online Library
Annals of neurology, 2006•Wiley Online Library
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 …
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 …
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. Ann Neurol 2006;60:32–44
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