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

Abstract

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.

Keywords:

• Endothelial cells
• Angiogenic factors
• Endothelial progenitor cells
• Immune response
• Spinal cord injury