Recombinant human SDF-1α administration accelerates aneurysm neck reendothelialization in rabbit saccular aneurysm after flow diverter treatment

Abstract

Reendothelialization in the aneurysm neck is pivotal to vascular repair for intracranial aneurysm after flow diverter (FD) implantation. Recombinant human stromal cell-derived factor 1α (rhSDF-1α) is a vital chemoattractant to stem cells and potentially facilitates reendothelialization. Here, we sought to investigate the therapeutic effects of intravenous administration of rhSDF-1α and uncover its potential mechanism for promoting aneurysm neck reendothelialization. Recombinant pET32a- 186 plasmid was transformed into Escherichia coli to produce the rhSDF-1α protein with biological activity. FD was implanted into the elastase-induced saccular aneurysm in New Zealand white rabbits. rhSDF-1α (50 μg/kg/day) was intravenously administrated for consecutive 7 days after FD implantation. After these procedures, aneurysms were harvested after 2 or 4 weeks. Scanning electron microscopy was used to measure the neointima thickness and count the endothelial-like cells at aneurysm neck. Four weeks later, the mRNA levels of endothelial markers in the neointima at aneurysm neck were examined. Migration assay showed that rhSDF-1α could induce migration of endothelial progenitor cells in a dose-dependent manner. Two weeks after stent implantation, follow-up angiography showed partial aneurysm occlusion in one of each group and total aneurysm occlusion in 17 saccular aneurysm rabbits (9 of the rhSDF-1α group and 8 of the control group). No significant change of neointima thickness at aneurysm neck was observed. Intriguingly, more endothelial-like cells were observed at aneurysm neck in the rhSDF-1α group at 2 weeks (55 vs 13 cells per high-power field) and 4 weeks (104 vs 60 cells per high-power field). The mRNA levels of Tie-2, VE-cadherin, KDR and E-selectin were significantly enhanced compared with those of the control group. These results showed that intravenous administration of rhSDF-1α can accelerate reendothelialization in the aneurysm neck after FD implantation. Our study reveals an important role of rhSDF-1α in inducing aneurysm occlusion and suggests that it achieves its function through modulating the reendothelialization.