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J Neurophysiol 84: 591-595, 2000;
0022-3077/00 $5.00
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The Journal of Neurophysiology Vol. 84 No. 1 July 2000, pp. 591-595
Copyright ©2000 by the American Physiological Society

RAPID COMMUNICATION

Embryonic Cord Transplants in Peripheral Nerve Restore Skeletal Muscle Function

Christine K. Thomas,1 Daniel E. Erb,2 Robert M. Grumbles,1 and Richard P. Bunge1

 1The Miami Project to Cure Paralysis and Department of Neurological Surgery, University of Miami School of Medicine, Miami 33136; and  2Division of Physical Therapy and Department of Orthopedics and Rehabilitation, University of Miami School of Medicine, Miami, Florida 33124

Thomas, Christine K., Daniel E. Erb, Robert M. Grumbles, and Richard P. Bunge. Embryonic Cord Transplants in Peripheral Nerve Restore Skeletal Muscle Function. J. Neurophysiol. 84: 591-595, 2000. The rapid atrophy of skeletal muscle after denervation severely compromises efforts to restore muscle function. We have transplanted embryonic day 14-15 (E14-E15) ventral spinal cord cells into adult Fischer rat tibial nerve stump to provide neurons for reinnervation. Our aim was to evaluate medial gastrocnemius reinnervation physiologically because this transplant strategy will only be effective if the reinnervated muscle contracts, generates sufficient force to induce joint movement, and is fatigue resistant enough to shorten repeatedly. Twelve weeks posttransplantation, brief duration electrical stimuli applied to the transplants induced medial gastrocnemius contractions that were strong enough to produce ankle movement in 4 of 12 rats (33%). The force of these four "low-threshold" reinnervated muscles and control muscles declined only gradually during five hours of intermittent, supramaximal stimulation and without depression of EMG potential area, which is strong evidence of functional neuromuscular junctions and fatigue resistant muscles. Sectioning of the medial gastrocnemius nerves confirmed that these contractions were innervation dependent. Weakness in low-threshold reinnervated muscles (8% control force) related to incomplete reinnervation, reductions in muscle fiber size, specific tension, and/or the presence of nonfunctional neuromuscular junctions. Muscle reinnervation achieved using this novel transplantation strategy may salvage completely denervated muscle and may provide the potential to evoke limb movement when injury or disease precludes or delays peripheral axon regeneration.




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D. C. Yohn, G. B. Miles, V. F. Rafuse, and R. M. Brownstone
Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy
J. Neurosci., November 19, 2008; 28(47): 12409 - 12418.
[Abstract] [Full Text] [PDF]


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