Neurotrophic factors improve muscle reinnervation from embryonic neurons.
Motoneurons die in diseases like amyotrophic lateral sclerosis and after spinal cord trauma, inducing muscle denervation. We tested whether transplantation of embryonic cells with neurotrophic factors into peripheral nerve of adult rats improves muscle reinnervation and motor unit function more than cells alone. One week after sciatic nerve section, embryonic ventral spinal cord cells were transplanted into the tibial nerve with or without glial cell line-derived neurotrophic factor, hepatocyte growth factor, and insulin-like growth factor-1. These cells represented the only neuron source for muscle reinnervation. Ten weeks after transplantation, all medial gastrocnemius muscles contracted in response to electrical stimulation of cell transplants with factors. Only 80% of muscles responded with cells alone. Factors and cells resulted in survival of more motoneurons and reinnervation of more muscle fibers for a given axon (motor unit) number. Greater reinnervation from embryonic cells may enhance muscle excitation by patterned electrical stimulation.
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Gizelda T B
GT
Casella
Vania W
VW
Almeida
Robert M
RM
Grumbles
Yang
Y
Liu
Christine K
CK
Thomas
D000818:Animals; D001369:Axons / Q000502:physiology; D002452:Cell Count; D002470:Cell Survival; D004576:Electromyography; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009046:Motor Neurons / Q000637:transplantation*; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000166:cytology / Q000294:innervation*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D033581:Stem Cell Transplantation
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I