The Promoting Effects of Activated Olfactory Ensheathing Cells on Angiogenesis after Spinal Cord Injury Through the PI3K/Akt Pathway
Abstract ObjectiveThe aim of this study was to investigate the pro-angiogenic potential of olfactory ensheathing cells (OECs) activated by curcumin (CCM) and lipopolysaccharide (LPS) and the possible underlying mechanisms. MethodsVascular endothelial cells or tissues were cultured and treated with conditioned medium (CM) extracted from the activated through the addition of LPS and CCM or unactivated OECs. Concomitantly, the pro-angiogenic potential of OECs was assessed in vitro by aortic ring sprouting assay, endothelial wound healing assay, CCK-8 assay and tube formation assay. Subsequently, the OECs were co-cultured with endothelial cells to evaluate their promoting effect on the proliferation and migration of endothelial cells following undergoing a mechanical scratch. Moreover, the spinal cord injury (SCI) model in rats was established, and the number of endothelial cells and vascular structure in the injured area after SCI was observed with OECs transplantation. Finally, the underlying mechanism was investigated by western blot analysis of phosphorylated kinase expression with or without the MK-2206 (Akt-inhibitor). ResultThe present results showed that the activated OECs can effectively promote the proliferation, migration and vessel-like structure formation of vascular endothelial cells. Strikingly, several pro-angiogenic growth factors such as VEGF-A and PDGF-AA, which facilitate vessel formation, were found to be significantly elevated in CM. In addition, the PI3K/Akt signaling pathway involved in pro-angiogenic event caused by activated OEC CM, displaying higher phosphorylation levels in cells. On contrary, the delivery of MK2206 can effectively abrogate all the positive effects. ConclusionsOECs activated by LPS and CCM, have a strong pro-angiogenesis effect, and can effectively promote angiogenesis and improve the injury microenvironment when transplanted in injured spinal cord. This potentiated ability of OECs to pro-angiogenesis is likely mediated through the PI3K/Akt pathway.