Search

Promising treatments for upper motor neuron disease are emerging in which motor function is restored by brain–computer interfaces and functional electrical stimulation. At present, such technologies and procedures are not applicable to lower motor neuron disease. We propose a novel therapeutic strategy for lower motor neuron disease and injury integrating neural stem cell transplantation with our new functional electrical stimulation control system. In a rat sciatic nerve transection model, we transplanted embryonic spinal neural stem cells into the distal stump of the peripheral nerve to reinnervate denervated muscle, and subsequently demonstrated that highly responsive limb movement similar to that of a healthy limb could be attained with a wirelessly powered two-channel neurostimulator that we developed. This unique technology, which can reinnervate and precisely move previously denervated muscles that were unresponsive to electrical stimulation, contributes to improving the condition of patients suffering from intractable diseases of paralysis and traumatic injury.

Neural cell transplantation targeting peripheral nerves is a potential treatment regime for denervated muscle atrophy. This study aimed to develop a new therapeutic technique for intractable muscle atrophy by the xenotransplantation of neural stem cells derived from pig fetuses into peripheral nerves. In this study, we created a denervation model using neurotomy in nude rats and transplanted pig-fetus-derived neural stem cells into the cut nerve stump. Three months after transplantation, the survival of neural cells, the number and area of regenerated axons, and the degree of functional recovery by electrical stimulation of peripheral nerves were compared among the gestational ages (E 22, E 27, E 45) of the pigs. Transplanted neural cells were engrafted at all ages. Functional recovery by electric stimulation was observed at age E 22 and E 27. This study shows that the xenotransplantation of fetal porcine neural stem cells can restore denervated muscle function. When combined with medical engineering, this technology can help in developing a new therapy for paralysis.

Motoneuron transplantation into peripheral nerves undergoing Wallerian degeneration may have applications in treating diseases causing muscle paralysis. We investigated whether functional reinnervation of denervated muscle could be achieved by early or delayed transplantation after denervation. Adult rats were assigned to six groups with increasing denervation periods (0, 1, 4, 8, 12, and 24 weeks) before inoculation with culture medium containing (transplantation group) or lacking (surgical control group) dissociated embryonic motoneurons into the peroneal nerve. Electrophysiological and tissue analyses were performed 3 months after transplantation. Reinnervation of denervated muscles significantly increased relative muscle weight in the transplantation group compared with the surgical control group for denervation periods of 1 week (0.042% ± 0.0031% vs. 0.032% ± 0.0020%, respectively; p = 0.009), 4 weeks (0.044% ± 0.0069% vs. 0.026% ± 0.0045%, respectively; p = 0.0023), and 8 weeks (0.044% ± 0.0029% vs. 0.026% ± 0.0008%, respectively; p = 0.0023). The ratios of reinnervated muscle contractile forces to naive muscle in the 0, 1, 4, 8, and 12 weeks transplantation groups were 3.79%, 18.99%, 8.05%, 6.30%, and 5.80%, respectively, indicating that these forces were sufficient for walking. The optimal implantation time for transplantation of motoneurons into the peripheral nerve was 1 week after nerve transection. However, the neurons transplanted 24 weeks after denervation survived and regenerated axons. These results indicated that there is time for preparing cells for transplantation in regenerative medicine and suggested that our method may be useful for paralysed muscles that are not expected to recover with current treatment.

Peripheral nerve disconnections cause severe muscle atrophy and consequently, paralysis of limbs. Reinnervation of denervated muscle by transplanting motor neurons and applying Functional Electrical Stimulation (FES) onto peripheral nerves is an important procedure for preventing irreversible degeneration of muscle tissues. After the reinnervation of denervated muscles, multiple peripheral nerves should be stimulated independently to control joint motion and reconstruct functional movements of limbs by the FES. In this study, a wirelessly powered two-channel neurostimulator was developed with the purpose of applying selective FES to two peripheral nerves&mdash, the peroneal nerve and the tibial nerve in a rat. The neurostimulator was designed in such a way that power could be supplied wirelessly, from a transmitter coil to a receiver coil. The receiver coil was connected, in turn, to the peroneal and tibial nerves in the rat. The receiver circuit had a low pass filter to allow detection of the frequency of the transmitter signal. The stimulation of the nerves was switched according to the frequency of the transmitter signal. Dorsal/plantar flexion of the rat ankle joint was selectively induced by the developed neurostimulator. The rat ankle joint angle was controlled by changing the stimulation electrode and the stimulation current, based on the Proportional Integral (PI) control method using a visual feedback control system. This study was aimed at controlling the leg motion by stimulating the peripheral nerves using the neurostimulator.