Increase of sensitivity to mechanical stimulus after transplantation of murine induced pluripotent stem cell-derived astrocytes in a rat spinal cord injury model.

Object: Clinical use of autologous induced pluripotent stem cells (iPSCs) could circumvent immune rejection and bioethical issues associated with embryonic stem cells. Spinal cord injury (SCI) is a devastating trauma with long-lasting disability, and current therapeutic approaches are not satisfactory. In the present study, the authors used the neural stem sphere (NSS) method to differentiate iPSCs into astrocytes, which were evaluated after their transplantation into injured rat spinal cords.

Methods: Induced pluripotent stem cell-derived astrocytes were differentiated using the NSS method and injected 3 and 7 days after spinal contusion-based SCI. Control rats were injected with DMEM in the same manner. Locomotor recovery was assessed for 8 weeks, and sensory and locomotion tests were evaluated at 8 weeks. Immunohistological parameters were then assessed.

Results: Transplant recipients lived for 8 weeks without tumor formation. Transplanted cells stretched their processes along the longitudinal axis, but they did not merge with the processes of host GFAP-positive astrocytes. Locomotion was assessed in 3 ways, but none of the tests detected statistically significant improvements compared with DMEM-treated control rats after 8 weeks. Rather, iPSC transplantation caused even greater sensitivity to mechanical stimulus than DMEM treatment.

Conclusions: Astrocytes can be generated by serum treatment of NSS-generated cells derived from iPSCs. However, transplantation of such cells is poorly suited for repairing SCI.