Human umbilical cord blood-derived CD34(+) cells were used to elucidate the mechanisms underlying the beneficial effects exerted by cord blood cells in
spinal cord injury (SCI). Rats were divided into four groups: (1)
sham operation (
laminectomy only); (2)
laminectomy + SCI + CD34(-) cells (5 x 10(5) human cord blood lymphocytes and monocytes that contained <0.2% CD34(+) cells); (3)
laminectomy + SCI + CD34(+) cells (5 x 10(5) human cord blood lymphocytes and monocytes that contained approximately 95% CD34(+) cells); and (4)
laminectomy + SCI + saline (0.3 mL).
Spinal cord injury was induced by compressing the spinal cord for 1 min with an
aneurysm clip calibrated to a closing pressure of 55 g. CD34 cells or saline was administered immediately after SCI via the tail vein. Behavioral tests of motor function measured by maximal angle an animal could hold to the inclined plane were conducted at days 1 to 7 after SCI. The
triphenyltetrazolium chloride staining and
terminal deoxynucleotidyl transferase-mediated
deoxyuridine triphosphate-
biotin nick end labeling assay were also conducted after SCI to evaluate spinal cord
infarction and apoptosis, respectively. To elucidate whether
glial cell line-derived neurotrophic factor (
GDNF) or
vascular endothelial growth factor (
VEGF) can be secreted in spinal cord-injured area by the i.v. transplanted CD34(+) cells, analysis of spinal cord homogenate supernatants by specific
enzyme-linked
immunosorbent assay for
GDNF or immunofluorescence for
VEGF was conducted. It was found that systemic administration of CD34(+), but not CD34(-), cells significantly attenuated the SCI-induced hind limb dysfunction and spinal cord
infarction and apoptosis. Both
GDNF and
VEGF could be detected in the injured spinal cord after
transplantation of CD34(+), but not CD34(-), cells. The results indicate that CD34(+)
cell therapy may be beneficial in reversing the SCI-induced spinal cord
infarction and apoptosis and hindlimb dysfunction by stimulating the production of both
VEGF and
GDNF in a
spinal cord compression model.