Regenerative medicine for stroke patients has been attracting attention. However, the effects of rehabilitation after the cell transplantation have not been fully elucidated. The purpose of the present study was to investigate whether intensive gait-focused rehabilitation using a robotic orthosis after regenerative medicine improved gait function and induced plastic changes in cortical networks. The present study was conducted in a retrospective cohort study. We selected seven chronic stroke patients, those who had undergone adipose-derived mesenchymal stem cells (MSC) transplantation therapy after the onset of stroke and had been receiving adequate subsequent gait rehabilitation with a robot for more than 2 months. During hospitalization, each patient received at least 2 h of rehabilitation, including robotic-assisted gait training more than five times per week. As the assessments, gait performance and M1 seed-based resting state-functional connectivity (rs-FC) obtained by a magnetoencephalography were compared before and after hospitalization. After rehabilitation, cadence and spatial gait symmetry ratio were significantly improved, and a significant negative correlation was found between the changes in the gait symmetry ratio and the time from transplant to rehabilitation. Seed-based rs-FC in the beta band between the lesioned M1 and multiple brain regions (e.g., both frontal areas, ipsilateral postcentral gyrus) was significantly decreased after the rehabilitation. Significant negative correlations were also observed between the changes in the gait symmetry ratio and the changes in lesioned M1 seed-based rs-FC in the paracentral gyrus and regions associated with the default mode network. It was revealed that intensive gait-focused rehabilitation using a robotic orthosis improved gait function and induced plastic changes in the cortical networks. The improvements were significantly correlated with the timing of the start of rehabilitation after MSC transplantation.
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