Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in a mouse spinal cord injury (SCI) model. "Safe" iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT + serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPSderived neurospheres pre-evaluated as "unsafe" showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that preevaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.neural stem/progenitor cell | cell transplantation | regenerative medicine | remyelination | axonal regrowth

Recent studies have shown that scalp electroencephalogram (EEG) based brain-computer interface (BCI) has a great potential for motor rehabilitation in stroke patients with severe hemiplegia. However, key elements in BCI architecture for functional recovery has yet to be clear. We in this study focused on the type of feedback to the patients, which is given contingently to their motor-related EEG in a BCI context. The efficacy of visual and somatosensory feedbacks was compared by a two-group study with the chronic stroke patients who are suffering with severe motor hemiplegia. Twelve patients were asked an attempt of finger opening in the affected side repeatedly, and the event-related desynchronization (ERD) in EEG of alpha and beta rhythms was monitored over bilateral parietal regions. Six patients were received a simple visual feedback in which the hand open/grasp picture on screen was animated at eye level, following significant ERD. Six patients were received a somatosensory feedback in which the motor-driven orthosis was triggered to extend the paralyzed fingers from 90 to 50°. All the participants received 1-h BCI treatment with 12–20 training days. After the training period, while no changes in clinical scores and electromyographic (EMG) activity were observed in visual feedback group after training, voluntary EMG activity was newly observed in the affected finger extensors in four cases and the clinical score of upper limb function in the affected side was also improved in three participants in somatosensory feedback group. Although the present study was conducted with a limited number of patients, these results imply that BCI training with somatosensory feedback could be more effective for rehabilitation than with visual feedback. This pilot trial positively encouraged further clinical BCI research using a controlled design.

BDNF-mediated restoration of KCC2 expression underlies the suppression of spasticity and allodynia caused by rehabilitation.

Transplantation of neural stem/progenitor cells (NS/PCs) following the sub-acute phase of spinal cord injury (SCI) has been shown to promote functional recovery in rodent models. However, the types of cells most effective for treating SCI have not been clarified. Taking advantage of our recently established neurosphere-based culture system of ES cell-derived NS/PCs, in which primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibit neurogenic and gliogenic potentials, respectively, here we examined the distinct effects of transplanting neurogenic and gliogenic NS/PCs on the functional recovery of a mouse model of SCI. ES cell-derived PNS and SNS transplanted 9 days after contusive injury at the Th10 level exhibited neurogenic and gliogenic differentiation tendencies, respectively, similar to those seen in vitro. Interestingly, transplantation of the gliogenic SNS, but not the neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, and resulted in significant locomotor functional recovery after SCI. These findings suggest that gliogenic NS/PCs are effective for promoting the recovery from SCI, and provide essential insight into the mechanisms through which cellular transplantation leads to functional improvement after SCI.

These results indicate that self-directed training with a brain computer interface may induce activity- dependent cortical plasticity and promote functional recovery. This preliminary clinical investigation encourages further research using a controlled design.