Human Umbilical Cord Blood-Derived Cd34+ Cells May Attenuate Spinal Cord Injury by Stimulating Vascular Endothelial and Neurotrophic Factors

Abstract

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.

Protective effects of human umbilical cord blood stem cell intravitreal transplantation against optic nerve injury in rats

“…Our data demonstrated that the protective mechanisms of transplanted hUCBSCs are associated with continuous secretion of BDNF and GDNF in vivo of retina of optic nerve injury rats. Elevated levels of BDNF and GDNF by grafted stem cells may promote differentiation of the grafted cells into neural cells, inhibit apoptosis, improve angiogenesis, suppress an inflammatory infiltrate, and maintain grafted cell survival [31].…”

Stem Cells: Current Approach and Future Prospects in Spinal Cord Injury Repair

“…Kao et al reported that systemic administration of 95% pure CD34þ progenitor cells derived from UCBSCs attenuates spinal cord infarction and apoptosis as well as behavioral deficits in a standard rat compression SCI model. In addition, current investigation provides new evidence suggesting that CD34þ cell therapy may cause restoration of spinal cord function during SCI by stimulating both GDNF and VEGF production in injured spinal cords (Kao et al, 2008). In previous reported clinical use of UCBSC to treat a patients with a SCI , it was stated that transplantation of UCBSCs improved sensory perception and mobility in hip and thigh regions.…”

Mesenchymal Stem Cell Therapy for Apoptosis After Spinal Cord Injury

“…There have been an increasing number of studies suggesting that these hUCB derived-CD34 + cells can induce angiogenesis and endo/exogenous neurogenesis in stroke (Taguchi et al, 2004) and SCI (Kao et al, 2008). In addition, Chen et al (2008) recently showed that hUCB cells have the ability to secrete multiple neurotrophic factors.…”