TNF ‐α promotes survival and migration of MSC s under oxidative stress via NF ‐κB pathway to attenuate intimal hyperplasia in vein grafts

The oxidative stress caused by endothelial injury is involved in intimal hyperplasia ( IH ) in vein grafts. Mesenchymal stem cells ( MSC s) can home to injured intima and promote endothelial repair. However, MSC apoptosis is increased accompanied by decreased functional activity under oxidative stress. Thus, we investigate whether tumour necrosis factor‐α ( TNF ‐α) can promote the survival and activity of MSC s under oxidative stress to reduce IH more effectively, and establish what role the NF ‐κB pathway plays in this. In this study, we preconditioned MSC s with TNF ‐α ( TNF ‐α‐PC MSCs) for 24 hrs and measured the activation of the IKK / NF ‐κB pathway. EdU and transwell assays were performed to assess proliferation and migration of TNF ‐α‐PC MSCs. Apoptosis and migration of TNF ‐α‐ PC MSC s were evaluated in conditions of oxidative stress by analysis of the expression of Bcl‐2 and CXCR 4 proteins. TNF ‐α‐ PC MSC s were transplanted into a vein graft model, so that cell homing could be tracked, and endothelial apoptosis and IH of vein grafts were measured. The results demonstrated that TNF ‐α promotes proliferation and migration of MSC s. Furthermore, survival and migration of TNF ‐α‐ PC MSC s under oxidative stress were both enhanced. A greater number of MSC s migrated to the intima of vein grafts after preconditioning with TNF ‐α, and the formation of neointima was significantly reduced. These effects could be partially abolished by IKK XII ( NF ‐κB inhibitor). All these results indicate that preconditioning with TNF ‐α can promote survival and migration of MSC s under oxidative stress via the NF ‐κB pathway and thus attenuate IH of vein grafts.