Combined demyelination plus Schwann cell transplantation therapy increases spread of cells and axonal regeneration following contusion injury

Abstract

Several cell populations have been shown to provide a permissive environment for axonal extension following transplantation to injury sites. The limited spread of transplanted cells from implantation sites in the mature CNS, and the superior substrate and trophic environment that they provide, likely contribute to the fact that few transplantation-based therapies have elicited axonal extension beyond the transplant. The aim of this study was to determine whether (1) regions of demyelination cranial and caudal to a spinal cord injury site would improve the spread of Schwann cells transplanted into the site of injury, and (2) whether this combination therapy was associated with improved anatomical regeneration. Three days following contusion injury, anti-galactocerebroside antibodies plus complement proteins were injected into the dorsal column cranial and caudal to the injury site, resulting in complete and well defined regions of demyelination that extended 8 mm either side of the injury site. One day later, naïve Schwann cells in suspension were injected into the contusion site. Transplanted Schwann cells homogeneously redistributed throughout the contusion site and the adjacent regions of demyelination cranial and caudal to the contusion site, providing a long-distance prospective path for repair that was free of myelin and contained transplanted cells. Animals that received demyelination plus transplantation therapy, but not untreated or single-treatment groups, exhibited robust axonal regeneration beyond the contusion site within the treated dorsal column. Axonal regeneration in these animals was not associated with an improvement in locomotor ability. These findings suggest that this combination therapy may overcome a central limitation of transplant strategies in which the permissive environment provided remains at the implantation site.