Evidence for proangiogenic cellular and humoral systemic response in patients with acute onset of spinal cord injury.

CONTEXT/OBJECTIVE: Traumatic spinal cord injury (SCI) leads to disruption of local vasculature inducing secondary damage of neural tissue. Circulating endothelial progenitor cells (EPCs) play an important role in post-injury regeneration of vasculature, whereas endothelial cells (ECs) reflect endothelial damage. METHODS: Twenty patients with SCI were assessed during the first 24 hours, at day 3, and day 7 post-injury and compared to 25 healthy subjects. We herein investigated EPC and EC counts by flow cytometry as well as the levels of soluble factors (SDF-1, HGF, VEGF, Ang2, EGF, endoglin, PLGF, FGF-2, ET-1, BDNF, IGF-1) regulating their migration and proangiogenic function. To better characterize peripheral blood (PB) cells, global gene expression profiles of PB-derived cells were determined using genome-wide RNA microarray technology. RESULTS: We found significantly higher EPC (CD34(+)/CD133(+)/VEGFR2(+)) as well as EC (VEGFR2(+)) count in PB of patients with SCI within 7 days post-injury and the increased HGF, ET-1, Ang2, EGF, and PLGF plasma levels. Global gene expression analysis revealed considerably lower expression of genes associated with both innate and adaptive immune response in PB cells in patients. CONCLUSION: Collectively, our findings demonstrate that SCI triggers bone marrow-derived EPC mobilization accompanied by increased circulating EC numbers. Significant changes in both chemoattractive and proangiogenic cytokines plasma levels occurring rapidly after SCI suggest their role in SCI-related regenerative responses to injury. Broadened knowledge concerning the mechanisms governing of human organism response to the SCI might be helpful in developing effective therapeutic strategies.