Regionally Specific Human Pre-Oligodendrocyte Progenitor Cells Produce Both Oligodendrocytes and Neurons after Transplantation in a Chronically Injured Spinal Cord Rat Model after Glial Scar Ablation
Nandadevi Patil, Patrick Walsh, Kailey Carrabre, Eric G Holmberg, Nicolas Lavoie, James R Dutton, Ann M Parr
Chronic spinal cord injury (SCI) is a devastating medical condition. In the acute phase after injury, there is cell loss resulting in chronic axonal damage and loss of sensory and motor function including loss of oligodendrocytes that results in demyelination of axons and further dysfunction. In the chronic phase, the inhibitory environment within the lesion including the glial scar can arrest axonal growth and regeneration and can also potentially affect transplanted cells. We hypothesized that glial scar ablation (GSA) along with cell transplantation may be required as a combinatorial therapy to achieve functional recovery, and therefore we proposed to examine the survival and fate of human induced pluripotent stem cell (iPSC) derived pre-oligodendrocyte progenitor cells (pre-OPCs) transplanted in a model of chronic SCI, whether this was affected by GSA, and whether this combination of treatments would result in functional recovery. In this study, chronically injured athymic nude (ATN) rats were allocated to one of three treatment groups: GSA only, pre-OPCs only, or GSA+pre-OPCs. We found that human iPSC derived pre-OPCs were multi-potent and retained the ability to differentiate into mainly oligodendrocytes or neurons when transplanted into the chronically injured spinal cords of rats. Twelve weeks after cell transplantation, we observed that more of the transplanted cells differentiated into oligodendrocytes when the glial scar was ablated compared with no GSA. Further, we also observed that a higher percentage of transplanted cells differentiated into V2a interneurons and motor neurons in the pre-OPCs only group when compared with GSA+pre-OPCs. This suggests that the local environment created by ablation of the glial scar may have a significant effect on the fate of cells transplanted into the injury site.