Regenerative potential of leptomeningeal-derived oligodendrocytes in rat model of spinal cord injury

Transplantation of oligodendrocytes is a promising avenue to therapies of demyelinating disorders. We have established an efficient multi-step protocol to induce oligodendrocyte differentiation from a recently described population of Leptomeningeal Stem Cells (LeSCs). With this study we want to asses regenerative and reparative potential of transplanted LeSCs in two models of spinal cord lesion associated to demyelination. The first model was based on parenchymal injection lysophosphatidylcholine (LPC) in rat spinal cord (n=11). GFP-labelled LeSCs-derived oligodendrocyte precursors (GFP-LeSC-OPCs, 200,000 cells/spinal cord) were transplanted 7 days after LPC treatment. By confocal microscopy at days 1 and 7 after transplantation (dpt) we observed GFP-LeSC-OPCs expressing markers of either proliferation, neural progenitors or differentiation. The second model was contusive spinal cord injury (SCI). Here we transplanted 400,000 GFP-LeSC-OPCs at the site of contusion 6 days after injury (dpi). Locomotor evaluation was assessed by the Basso, Beattie, and Bresnahan (BBB) rating scale and subscale, Catwalk analysis and electrophysiology. Measurements were taken 1 and 6 dpi, and at several time points between 1 and 56 dpt. From 3 weeks after GFP-LeSC-OPCs transplantation (n=11), rats showed significant improvement in locomotion subparameters compared to controls (n=12) in BBB score. Catwalk analysis showed significant differences at 56 dpt whereas electrophysiological evaluation did not. In depth histochemical and functional analysis of transplanted cells in the two models is in progress. In conclusion we show that LeSCs-derived oligodendrocyte precursors transplanted in lesioned spinal cords survive and proceed toward differentiation and can promote functional recovery.