Intraspinal cord graft of autologous activated Schwann cells efficiently promotes axonal regeneration and functional recovery after rat's spinal cord injury.

摘要

Basic research in spinal cord injury (SCI) has made great strides in recent years, and some new insights and strategies have been applied in promoting effective axonal regrowth and sprouting. However, a relatively safe and efficient transplantation technique remains undetermined. This study, therefore, was aimed to address a question of how to graft Schwann cells to achieve the best possible therapeutic effects. To clarify the issue, the rats were subjected to spinal cord injury at T10. Autologous activated Schwann cells (AASCs) were obtained by prior ligation of saphenous nerve and subsequently isolated and purified in vitro and then grafted into spinal cord-injured rats via three different routes (group I: intravenous, group II: intrathecal and group III: intraspinal cord). Neurologic function was serially evaluated by Basso, Beattie, Bresnahan locomotor rating scale and footprint analysis. We also evaluated the migration of the transplanted cells at 2 weeks after transplantation. Using biotinylated dextran amine (BDA) anterograde tracing, we demonstrated that more regenerative axons of corticospinal tract (CST) surrounding the injured cavity in group III than those in the other two groups, and we also confirmed it further by quantitative analysis. The microenvironment surrounding the injured spinal cord has been improved to the greatest extent in group III, as determined by immunohistological staining. Relatively complete myelin sheaths and more neurofilaments in axons were found in groups II and III than those in group I under electron microscopy. The results showed that intraspinal cord injection of AASCs promoted recovery of hindlimb locomotor function of injured rats more efficiently than the other grafting routes. In addition, intact myelin sheaths and sufficient neurofilaments in axons were not adequate for full functional recovery after SCI, suggesting that reestablishment of normal synaptic connection is indispensable. The findings in this study strongly suggest that transplantation of AASCs directly into the spinal cord may be one of the promising candidates for potential scaffold for injured spinal cord, and such strategy of transplantation of AASCs could be hopeful to treat patients with SCI.