Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury.
BACKGROUND
Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells.


OBJECTIVE
We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls.


METHODS
Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis.


METHODS
Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally.


RESULTS
Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66).


CONCLUSIONS
Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques.
Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway St, MC 6342, Redwood City, CA 94063, USA. ivan.cheng@stanford.edu
Ivan
I
Cheng
Robert E
RE
Mayle
Christopher A
CA
Cox
Don Y
DY
Park
Robert L
RL
Smith
Ian
I
Corcoran-Schwartz
Karthikeyan E
KE
Ponnusamy
Rayshad
R
Oshtory
Matthew W
MW
Smuck
Raj
R
Mitra
Alexander I
AI
Kharazi
Eugene J
EJ
Carragee
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000166:cytology; D005865:Gestational Age; D006801:Humans; D007268:Injections, Epidural; D007278:Injections, Spinal; D007796:Laminectomy; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation*; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D033581:Stem Cell Transplantation; D016896:Treatment Outcome