Recovery from paralysis in adult rats using embryonic stem cells.
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.


CONCLUSIONS
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.
Deshpande
Deepa M
DM
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-6965, USA.
Kim
Yun-Sook
YS
Martinez
Tara
T
Carmen
Jessica
J
Dike
Sonny
S
Shats
Irina
I
Rubin
Lee L
LL
Drummond
Jennifer
J
Krishnan
Chitra
C
Hoke
Ahmet
A
Maragakis
Nicholas
N
Shefner
Jeremy
J
Rothstein
Jeffrey D
JD
Kerr
Douglas A
DA
D000367:Age Factors; D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured / Q000637:transplantation; D004594:Electrophysiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006085:Graft Survival; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation; D009416:Nerve Regeneration / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D010243:Paralysis / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*
D051100:Glial Cell Line-Derived Neurotrophic Factor