Progress and prospects of endothelial progenitor cell therapy in coronary stent implantation

Drug-eluting stents (DES) have been widely used to treat coronary artery disease (CAD) since their clinical use has significantly reduced the occurrence of in-stent restenosis (ISR) as compared with the initially applied bare-metal stents (BMS). However, analyses of long-term clinical outcome have raised concerns about the serious safety problem of DES, such as ISR caused by late or very late thrombosis. Various studies showed that those complications were associated with vascular endothelial injury/dysfunction or endothelialization delaying. Recently, through biological characterization of endothelial progenitor cells (EPCs), mechanistic understanding of rapid re-endothelialization of the vascular injury sites after coronary stenting has become possible and is a new research hotspot in the prevention of ISR and late/very late stent thrombosis. It has been well recognized that the formation of a functional endothelial layer from EPCs requires a coordinated sequence of multistep and signaling events, which includes cell mobilization, adhesion, migration and finally the differentiation to vascular endothelial cells (VECs). In this review, we summarize and discuss the currently relevant information about EPCs, the mechanism of DES interfering with the natural vascular healing process in preventing or delaying the formation of a functional endothelial layer, and EPCs-mediated acceleration of re-endothelialization at vascular injury sites. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1237-1247, 2016.