Optical control of muscle function by transplantation of stem cell-derived motor neurons in mice.
Damage to the central nervous system caused by traumatic injury or neurological disorders can lead to permanent loss of voluntary motor function and muscle paralysis. Here, we describe an approach that circumvents central motor circuit pathology to restore specific skeletal muscle function. We generated murine embryonic stem cell-derived motor neurons that express the light-sensitive ion channel channelrhodopsin-2, which we then engrafted into partially denervated branches of the sciatic nerve of adult mice. These engrafted motor neurons not only reinnervated lower hind-limb muscles but also enabled their function to be restored in a controllable manner using optogenetic stimulation. This synthesis of regenerative medicine and optogenetics may be a successful strategy to restore muscle function after traumatic injury or disease.
Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL) Institute of Neurology, London, UK.
J Barney
JB
Bryson
Carolina Barcellos
CB
Machado
Martin
M
Crossley
Danielle
D
Stevenson
Virginie
V
Bros-Facer
Juan
J
Burrone
Linda
L
Greensmith
Ivo
I
Lieberam
D000818:Animals; D001369:Axons / Q000502:physiology; D002460:Cell Line; D000075402:Channelrhodopsins; D004558:Electric Stimulation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D006614:Hindlimb; D007537:Isometric Contraction; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation* / Q000502:physiology*; D009416:Nerve Regeneration; D062308:Optogenetics; D012584:Sciatic Nerve / Q000502:physiology; D014162:Transfection; D019076:Transgenes
D000075402:Channelrhodopsins