Regenerative medicine strategies for chronic complete spinal cord injury

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

The prospects of regenerative medicine combined with rehabilitative approaches for chronic spinal cord injury animal models

Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury（SCI）.By contrast,there are still only a few studies have focused on the treatment of the chronically injured spinal cord,in which cell-based regenerative medicine seems less effective.Since the majority of SCI patients are in the chronic phase,representing a major challenge for the clinical application of cellbased regenerative medicine.Although combined therapies for the treatment of chronic SCI have attracted attention of researchers and its potential importance is also widely recognized,there had been very few studies involving rehabilitative treatments to date.In a recent study,we have demonstrated for the first time that treadmill training combined with cell transplantation significantly promotes functional recovery even in chronic SCI,not only in additive but also in synergistic manner.Even though we have succeeded to outline the profiles of recovery secondary to the combination therapy,the mechanism underlying the effects remain unsolved.In this review article,we summarize the present progress and consider the prospect of the cell-based regenerative medicine particularly combined with rehabilitative approaches for chronic SCI animal models.