Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: Long-term survival and functional recovery in canines

Spinal cord injury (SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues (aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of aSCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein 2-, 5-hydroxytryptamine-, choline acetyltransferase- and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in aSCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.