Optical Control of Muscle Function by Transplantation of Stem Cell–Derived Motor Neurons in Mice

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Science  04 Apr 2014:
Vol. 344, Issue 6179, pp. 94-97
DOI: 10.1126/science.1248523

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Optogenetics Applied to Motorneuron Control

Nerves damaged by disease or injury do not always regenerate. In such cases, therapies involving transplanted stem cells show some promise. However, the new neurons derived from transplanted cells cannot communicate with the central control systems that would normally regulate movement. To avoid the need for such communication, in a proof-of-principle study, Bryson et al. (p. 94; see the Perspective by Iyer and Delp) added optogenetic control to differentiation and transplantation of motor neurons. In the mouse, these engineered neurons were able to reestablish connections within a damaged sciatic nerve and, when activated by localized light stimulation, could drive muscle contractions.


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.

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