Transplanted neural progenitor cells survive and differentiate but achieve limited functional recovery in the lesioned adult rat spinal cord.
Endogenous repair after injury in the adult CNS is limited by a number of factors including cellular loss, inflammation, cavitation and glial scarring. Spinal cord neural progenitor cells (SCNPCs) may provide a valuable cellular source for promoting repair following spinal cord injury. SCNPCs are multipotent, can be expanded in vitro, have the capacity to differentiate into CNS cell lineages and are capable of long-term survival following transplantation.


OBJECTIVE
To determine the extent to which SCNPCs may contribute to spinal cord repair SCNPCs isolated from rat fetal spinal cord were expanded ex vivo and transplanted into the adult rat spinal cord after a dorsal column crush lesion.


RESULTS
The survival and distribution of transplanted cells were examined at 24 h, 1, 2 and 6 weeks after injury. Transplanted cells were identified at all time points, located mainly at the lesion perimeter, indicating good post-transplant cell survival. Furthermore, SCNPCs maintained their ability to differentiate in vivo, with approximately 40% differentiating into cells with a glial morphology, whilst 8% displayed a neural morphology. Transplanted animals were also assessed on a number of behavioral tasks measuring sensorimotor and proprioceptive function to determine the extent to which SCNPC transplants might attenuate lesion-induced functional deficits. SCNPCs failed to promote significant functional recovery, with a small improvement observed in only one of the four tasks employed, primarily related to improvements in sensory function. Tracing of the corticospinal tract and ascending dorsal column pathway revealed no regeneration of the axons beyond the lesion site.


CONCLUSIONS
These data indicate that, although transplanted SCNPCs show good survival in the spinal cord injury environment, combination with other treatment strategies is likely to be required for these cells to fully exert their therapeutic potential.
University of Cambridge, Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK. djw74@cam.ac.uk
Daniel J
DJ
Webber
Elizabeth J
EJ
Bradbury
Stephen B
SB
McMahon
Stephen L
SL
Minger
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D008297:Male; D009416:Nerve Regeneration; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*