Vascular Endothelial Growth Factor Enhanced the Angiogenesis Response of Human Umbilical Cord-Derived Mesenchymal Stromal Cells in a Rat Model of Radiation Myelopathy

The present study was designed to examine a synergistic role for VEGF and human umbilical cord-derived MSCs (UC-MSCs) therapy in a rat model of radiation myelopathy. UC-MSCs and VEGF were injected through the tail vein at 90, 97, 104 and 111 days post-irradiation. Behavioral tests were performed, and histological damage was examined. The microcirculation in the spinal cord was assessed using von Willebrand factor immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor and glial cell-derived neurotrophic factor in the spinal cord. The UC-MSCs processed with VEGF, including VEGF165-induced UC-MSC (iUC), VEGF and UC-MSCs (VEGF-UC), increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, raised the relative magnitude of spinal cord blood flow compared to UC-MSCs treatment alone. Our data provided the first evidence that vascular endothelial growth factor enhanced the angiogenesis response of human umbilical cord-derived mesenchymal stromal cells in a rat model of radiation myelopathy.