Pre-Differentiated Embryonic Stem Cell versus Olfactory Ensheathing Cell for Spinal Cord Regeneration after Compressive Injury in Rat

Abstract

Background: Transplantation approaches are interventions currently available to apply to the devastating problem of spinal cord injury (SCI). Olfactory ensheathing cell (OEC) and embryonic stem cell (ESC) are considered to be promising therapeutic strategies . In this study, we compared the potential use of OECs and neurally pre-differentiated ESCs in contusion spinal cord. Methods: OECs were harvested from olfactory bulb of rats and labeled with Hoescht 33342. ESCs were generated by using feeder free GFP positive CGR8 mouse ESCs and neurally pre-differentiation was induced by retinoic acid (RA) and characterized by different antibodies. SCI was induced by fogarty catheter at T8-T9 level in adult rats. Transplantations were performed 9 days after the injury. Rats were randomly divided into 3 main groups (neurally pre-differentiated ESC, OEC and media as control group). The recovery of gross motor function was evaluated using Basso-Beattie-Bresnahan (BBB) locomotor rating scale on the ninth day post injury and once per week thereafter for 4 weeks after cell transplantation. At 28 days after transplantation, histological assessment including transplanted cell detection in tissue, tissue sparing and myelinated axons was performed. Results: Following transplantation, a significant recovery of hindlimb function according to BBB scale was observed in rats in the transplanted groups compared to control and sham groups (p<0.05). There was no significant difference between transplanted groups four weeks after transplantation. OEC and ESC were found in the tissue after transplantation. In OEC group, many of OECs were detected around and within the cystic cavity that number of these cells was significantly higher in comparison with number of cells in ESC group (p< 0.001). In the site of injury, several cavities were produced that disrupted portions of the gray and white matters. The extent of tissue damage was more severe in the sham and control groups than the other groups. Significantly more spinal tissue was spared in OEC and ESC groups (P < 0.001). No significant difference in percentage of spared tissue was found between sham and control groups or transplanted groups. The percentage of myelinated area was greater in OEC group than in three other groups (p< 0.05) (Figure 5, A). Although the percentage of myelinated area was more in ESC group in comparison with non-treated groups, but this difference was not significant. Conclusion: It seems that using of combination of a myelinating cells like OEC or schwann cell and source of cells to replace dead cells like Mesenchymal or embryonic stem cells, better results can be obtained due to probable synergic effects of these cells.