Delayed Transplantation of Human Central Nervous System Stem Cells Into Spinal Cord Contusion Injured NOD-Scid Mice

Earlier studies have shown that human central nervous system stem cells(hCNS-SCns) grown as neurospheres, facilitate locomotor recovery in immunodeficient NOD-scid mice upon transplantation into a contusion induced spinal cord injury (SCI) 9 days post injury. The CD133+ hCNS-SCns derived from fetal brain using FACS analysis and grown as neurospheres can be expanded in defined serum free conditions, and differentiate into neurons or glia. In those studies, hCNS-SCns differentiated into myelinating oligodendrocytes and synapse forming neurons, suggesting there was integration of the human cells in the mouse thus a potential mechanism of locomotor recovery. Our hypothesis is that integration of hCNS-SCns in spinal cord injured mice will contribute to locomotor recovery, survive, and differentiate when transplant is delayed 30 days post SCI. In this study 75,000 hCNS-SCns were transplanted into NOD-scid mice 30 days post SCI. Locomotor assessments were conducted using open field testing (BBB, BMS), post injury horizontal ladder beam and CatWalk gait analysis. hCNS-SCns transplanted animals performed better on BBB and BMS tasks (X2, p0.05) than animals transplanted with hFibroblasts or vehicle controls. Von Frey hair testing was used to assess mechanical allodynia. Mice were sacrificed 16 weeks post transplantation. Further analyses of other behavioral tasks along with stereological quantification of human cell engraftment and migration at 16 weeks post transplantation, using an antibody to human cytoplasmic protein (SC121) are still in progress. The data suggests that delayed transplantation of hCNS-SCns can improve locomotor recovery and extend the interval at which cell based SCI therapies can be administered.