Cell Source in Stent Induced Restenosis

Abstract

Traditionally, restenotic neointimal hypercellularity has been attributed to migration and proliferation of vessel wall smooth muscle cells (SMC). This scheme has been challenged by findings of circulating blood SMC progenitors that contribute to the formation of vascular lesions. In stent restenosis (ISR) limits the long-term success of percutaneous treatments and is caused by excessive accumulation of SMC. The pathobiological events underlying ISR are poorly understood. Recently, human tissue obtained by atherectomy, retrieved from ISR and de-novo primary lesions, were compared by immunohistochemistry analysis. Interestingly, the presence of bone marrow derived endothelial progenitor cells and dendritic cells, as well as neural crest derived cells were found in all ISR atherectomy specimens. Furthermore, specific staining was significantly increased in ISR tissue compared to primary plaque. This suggests the recruitment of primarily extravascular cells within ISR neointimal formation. Sirolimus-eluting stents (SES) have lately emerged as an effective strategy to prevent ISR. Despite increasing clinical use, little is known about the mechanism by which locally delivered Sirolimus prevents ISR. Recently, Sirolimus was shown to potently inhibit human vascular progenitor cell outgrowth in-vitro. In-vivo, Sirolimus elicited an inhibitory effect on both SMC and endothelial progenitor cell incorporation at sites of wire-mediated vascular injury of bone marrow chimeric mice. This potent inhibitory effect of sirolimus on circulating SMC progenitor cells may mediate in part the clinical efficacy of SES.