Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells and Schwann cells

Abstract

Background: The most important objective of transplant studies in the injured spinal cord has been to provide a favorable environment for axonal growth. Moreover, the continuing discovery of new grafts is providing new potentially interesting transplant candidates. Our purpose was to observe the morphological and functional repair effects of the co-transplantation of neural stem cell (NSC), Schwann cells (SCs) and poly lactide-co-glycolide acid (PLGA) on the spinal cord injury of rats.

Methods: A scaffold of PLGA was fabricated. NSCs and SCs were cultured, with the NSCs labeled with 5-bromodeoxyuridine, and the complex of NSC/PLGA or NSC + SCs/PLGA were constructed. Thirty-six Wistar rats were randomly divided into three groups: group A (transplantation of PLGA), group B (transplantation of NSC/PLGA) and group C (transplantation of NSC + SCs/PLGA). The 3 mm length of the right hemicord was removed under the microscope in all rats. The PLGA or the complex of PLGA-cells were implanted into the injury site. Basso-Beattie-Bresnahan (BBB) locomotion scores, motor and somatosensory evoked potential of lower limbs were examined to learn the rehabilitation of sensory and motor function at 4 weeks, 8 weeks, 12 weeks and 24 weeks after injury. All the recovered spinal cord injury (SCI) tissues were observed with HE staining, immunohistochemistry, and transelectronmicroscopy to identify the survival, migration and differentiation of the transplanted cells and the regeneration of neural fibres at 4 weeks, 8 weeks, 12 weeks and 24 weeks after injury.

Results: (1) From 4 weeks to 24 weeks after injury, the BBB locomotion scores of cell-transplanted groups were better than those of the non-cell-transplanted group, especially group C (P < 0.05). The amplitudes of the somatosensory evoked potential (SEP) and motor-evoked potential (MEP) were improved after injury in groups B and C, but the amplitude of SEP and MEP at 4 weeks was lower than that at 12 weeks and 24 weeks after injury. Compared with group B, the amplitude of SEP and MEP in group C was improved. The amplitude of SEP and MEP was not improved after injury in group A. (2) HE staining revealed the volume of the scaffold decreased and the number of cells in the scaffold increased. Newly-grown capillaries also could be seen. Immunohistochemistry staining showed the transplanted NSCs could survive and migrate until 24 weeks and they could differentiate into neurons and oligodendrocytes. The regenerated axons were observed in the scaffold-cell complex with transelectronmicroscopy. The above manifestations were more extensive in group C.

Conclusions: The transplanted NSC can survive and migrate in the spinal cord of rats up to 24 weeks after injury, and they can differentiate into various neural cells. Co-transplantation of cells/PLGA can promote the functional recovery of the injured spinal cord. The effect of co-transplanting NSC + SCs/PLGA is better than transplanting NSC/PLGA alone.