Inhibitory effects of mesenchymal stem cells in intimal hyperplasia after balloon angioplasty

Objective: Intimal hyperplasia is a major cause of restenosis after arterial bypass and balloon angioplasty. Induction of rapid re-endothelialization has been proposed to reduce intimal hyperplasia. The aim of this study was to evaluate the inhibitory effect of mesenchymal stem cells on intimal hyperplasia. Methods: Male New Zealand white rabbits were fed 1% cholesterol diets from 1 week before balloon angioplasty to the day of harvest. After dissection of rabbit carotid arteries, balloon angioplasty was performed with a 2F Fogarty embolectomy catheter. The injured carotid artery was coated with a mixture of 7 x 10(6) human umbilical cord mesenchymal stem cells (HUC-MSCs) and fibrin matrix. The carotid arteries were harvested 2, 4, and 8 weeks thereafter, and immunofluorescent staining and quantitative real-time polymerase chain reaction analysis were performed. Results: The intima/media ratio was significantly reduced in the group treated with HUC-MSCs compared with the nontreated group (Student t-tests, * P < .05). The area of re-endothelialization was significantly higher (Student t-tests, * P < .05) in the group treated with HUC-MSCs than in the nontreated group. Expression of angiogenic genes such as vascular endothelial growth factor, platelet-derived growth factor, kinase insert domain receptor 1, angiopoietin 1, and angio-associated migratory cell protein was increased (analysis of variance, P < .05) in the group treated with HUC-MSCs relative to the nontreated group. Conclusions: Our study showed that HUC-MSCs reduce the formation of intimal hyperplasia through rapid re-endothelialization. This resultmight be applied to development of stemcell-coated stents as well as to development of a stem cell-containing sheet coat for inhibition of intimal hyperplasia after angioplasty or surgery. Clinical Relevance: The inhibitory effect of mesenchymal stem cells on intimal hyperplasia might be applied to development of stem cell-coated stents as well as to development of a stem cell-containing sheet coat for inhibition of intimal hyperplasia after angioplasty or surgery.