Skin-Derived Precursors Differentiated into Schwann Cells (SKP-SCs) and Transplanted Eight Weeks Post-Spinal Cord Contusion Improve Recovery of Motor Function and Bladder Pathology

Background: Cell transplantation has emerged as an exciting therapeutic approach for spinal cord injury (SCI) in animals and unproven cell treatments in humans are performed in many centers worldwide. However, to this date two clinical trials in humans have been initiated, and the best candidate cell for transplantation after SCI is intensely debated. The overwhelming majority of cell transplantation studies in animals have been performed in subacute models of SCI (1-2 wks post-injury). Efficacy in chronic models of SCI (6-12 wks post-injury) is rare, and thus the applicability of this approach for the many chronic SCI patients is questionable – yet these are the majority of “stem cell tourists”. Many stem cells transplants would require immunosuppression to prevent rejection and some may bear the risk of embryonic tumor formation. Our laboratories champions Schwann cells generated from skin precursor cells (SKP-SCs) because they may be derived autologously (ie. from the patients’ own skin). We have previously shown that Schwann cells differentiated from skin-derived precursors (SKP-SCs), when transplanted 7 days after contusion injury, promote histological repair and functional recovery in rats. Methods: Here, we evaluated SKP-SCs in a chronic model of thoracic SCI. A T9/10 contusive SCI was induced in rats using an electromagnetic impactor that delivers reproducible bruises of the spinal cord. The animals recovered over the ensuing 8 weeks (could walk with impaired co-ordination), at which time they were grouped to receive a transplant of SKP-SCs or media control treatment. Behavioral recovery was then assessed until post-injury week 27, and the animals were sacrificed at post-injury week 29 and their spinal cords were evaluated histologically. Results: Animals treated with SKP-SCs continued to improve hindlimb locomotion, which reached significance in weeks 19 and 21 compared to the controls. The transplanted cells survived, integrated into the host tissue, modified the glial scar, and created a lesion site permissive to nerve regeneration, as evidenced by the massive extension of thousands of nerve fibers through the lesion sites which are empty cavities in controls. The pathological thickening of the bladder wall characteristic of a bladder dysfunctions was also reduced in the SKP-SC treated rats. Conclusions: SKP-SCs transplanted 8 weeks post-injury survive and bridge the chronic SCI injury site, facilitate nerve fibre regeneration and remyelination (re-insulation) of these nerve fibres, and promote locomotor recovery. Success with cell transplantation approaches in experimental models of chronic SCI is rare. Our results highlight the potential of SKP-SCs (which may be derived autologously, obviating the need for immunosuppresion) as a transplantation strategy for chronically injured SCI patients supporting the rationale to trial these cells in humans. Supported by CIHR, Canadian Stem Cell Network, and Rick Hansen Foundation.