Realizing the maximum potential of Schwann cells to promote recovery from spinal cord injury

Transplantation of Schwann cells (SCs) has been extensively investigated as a therapeutic intervention in rodent models of spinal cord injury (SCI). Here we review both strengths and weaknesses of this approach and discuss additional strategies for maximizing the potential of SCs to repair the injured spinal cord. With no additional treatments, SCs were consistently shown to provide a bridge across the lesion site, supporting the ingrowth of sensory and propriospinal axons, to myelinate axons and to decrease the size of cavities formed after injury. Supraspinal axons did not, however, grow onto the bridge, axons failed to traverse the caudal SC-host cord interface and transplanted SC survival was poor. More recent studies have shown that the potential of SC transplantation as a therapeutic approach can be strongly enhanced by combining additional strategies For example, combining SC transplantation with elevation of cAMP levels resulted in growth of brainstem axons into the SC graft and caudal to the lesion and in significant improvements in locomotion. Axon growth (and functional improvement) have been increased by strategies to raise neurotrophin levels, either by injection or by genetic modification of the SCs before transplantation. A major problem in maximizing SC potential in injured cord has been in achieving good integration of the transplanted cells with the adjacent cord parenchyma. Several previous studies suggested an ability of SCs to migrate extensively in CNS tissue when astroctyes were absent and to myelinate CNS axons. Furthermore, in some cases involving very limited injury, SCs migrated and integrated well even in the presence of host astrocytes. Consistent with these observations, treatments with an enzyme, chondroitinase, to modify the SC-astrocyte interface surrounding the graft, have shown much promise. Very new studies have shown that SCs derived from SC precursors show a higher ability to survive, integrate well with host tissue and support brainstem axon growth into and beyond the graft, confirming the innate promise of SCs in spinal cord repair. We review one clinical trial already underway in Iran testing SC transplantation in patients with SCI. Finally, we briefly describe a protocol, adaptable to the principles of good manufacturing practice, for generating large numbers of human SCs. Overall, the available evidence suggests that SCs, especially when used in combination with other treatments, offer one of the best hopes we have today of devising an effective treatment for spinal cord repair.